IndraLab

Statements



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"USP22 silencing inhibits the tumor cell proliferation [76]."

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"By contrast, USP22 was overexpressed in NPC cells and promoted the proliferation of NPC."

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"We found that SOS1 silencing effectively reversed USP22-induced changes in cell proliferation, migration, invasion, and apoptosis in vitro."

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"Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status."

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"Previous studies showed that USP22 enhances cancer cell proliferation through interaction with Rb and p53."

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"Our previous studies have confirmed that defects in USP22 can not only cause cell cycle arrest in G0/G1 phase, but also inhibit apoptosis and promote tumor cell proliferation [XREF_BIBR]."

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"USP22 has been shown to promote the proliferation of human non small cell lung cancer cell H1129 and human bladder cancer cell EJ by facilitating cell cycle progression, which was supported by the observed G1 phase arrest and concomitant reduction in the S and G2/M phase when USP22 was depleted [XREF_BIBR, XREF_BIBR]."

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"Moreover, there was no synergistic effect on cell proliferation when both USP22 and YAP were depleted (XREF_FIG; P> 0.05), suggesting that USP22 promoted cell proliferation largely through YAP."

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"USP22 silencing by shRNA inhibits proliferation, induces apoptosis and arrests cells at the G0/G1 phases in NSCLC cells and curbs human NSCLC tumor growth in a mouse xenograft model."

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"Moreover, EdU assay results showed that USP22 knockdown significantly reduced proliferation of BGC-823 and HGC-27 cells compared with the controls (Figure 2D)."

sparser
"Together, these data showed that USP22 silencing inhibited the proliferation of ATC cells in vitro ."

sparser
"Consistently, we demonstrated that USP22 silencing inhibited the proliferation of human ATC cells (8505C and CAL-62)."

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"USP22 depletion inhibits the proliferation of ATC cells in vitro."

sparser
"USP22 Silencing Inhibits Proliferation and Induces Apoptosis and Cell Cycle Arrest in NSCLC Cells."

sparser
"USP22 silencing inhibits GC cells proliferation."

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"Downregulation of USP22 inhibited OS cell proliferation, invasion, and EMT in vitro."

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"USP22 downregulation inhibited OS cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro."

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"We also suggested that downregulation of USP22 inhibited OS cell proliferation and invasion in vitro."

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"As shown in Figure XREF_FIG to XREF_FIG, silencing USP22 significantly inhibited proliferation and generated a smaller number of colonies in Bel/Fu cells."

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"Moreover, USP22 down-regulation in HUVECs led to decreased proliferation, angiogenesis, vasodilation, apoptosis, and systolic function."
USP22 affects SIRT1
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USP22 binds SIRT1.
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"Our studies suggest that SIRT1 and CCNB1 interact with USP22 through different regions."

sparser
"In this study, USP22 directly interacted with SIRT1 and positively regulated SIRT1 protein expression."

sparser
"These findings suggest that the co-expression of USP22 and SIRT1 is significantly associated with unfavorable HCC progression."

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"USP22 can also form a complex with the histone deacetylase SIRT1, which serves a similar repressive action on Sox2."

sparser
"Additionally, to better understand the role of USP22-SIRT1 axis in ferroptosis-induced cell death, the effects of overexpression or knockdown of SIRT1 on ferroptosis signaling pathway were examined using Western blot analysis ( xref )."

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"USP22 directly interacts with SIRT1 based on the co-immunoprecipitation assay."

sparser
"In our previous study, USP22 bound to SIRT1 and subsequently activated the AKT pathway, increasing the expression of MRP1 to induce 5-FU resistance in HCC cells [ xref ]."

sparser
"SIRT1 physically interacts with USP22 as a mediator of USP22."

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"These results indicate that USP22 directly interacts with SIRT1 and contributes to stabilization of SIRT1 protein in FLT3-ITD AML cells."

sparser
"USP22 Interacts with SIRT1 and Maintains Its Protein Expression."
USP22 binds SIRT1 and FLT3. 1 / 1
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sparser
"We show that USP22 directly interacts with SIRT1 in FLT3-ITD AML cells in a FLT3-kinase-independent manner."
USP22 inhibits SIRT1.
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USP22 inhibits SIRT1. 5 / 9
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"USP22 depletion enhanced Sirt1 degradation and displayed combined effects with AGEs to further promote FN and TGF-beta1 expression."

sparser
"USP22 Inhibits SIRT1 to Regulate Ferroptosis-Induced Cardiomyocyte Death."

sparser
"Moreover, we found that USP22 inhibited the SIRT1 gene to regulate ferroptosis-induced cardiomyocyte death."

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"Additionally, SIRT1 instability caused by loss of USP22, a deubiquitinating enzyme that stabilizes SIRT1, is associated with the defective embryogenesis in USP22 null mice [XREF_BIBR]."

eidos
"USP22 Inhibits SIRT1 to Regulate Ferroptosis-Induced Cardiomyocyte Death A previous study has shown that USP22 possesses the ability to stabilize SIRT1 by the process of deubiquitination ( Lin et al ., 2012 ) ."
USP22 deubiquitinates SIRT1.
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USP22 deubiquitinates SIRT1. 9 / 9
1 | 1 7

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"For instance, HULC can upregulate the expression of the ubiquitin specific peptidase 22 (USP22) protein by suppressing miR-6825-5p, miR-6845-5p, and miR-6886-3p at the epigenetic or transcriptional level in HCC cells; USP22 enhances the HULC induced deubiquitination of Sirt1 and stabilizes it, and Sirt1 stability induces the autophagy of HCC cells, thus increasing the resistance of HCC cells to oxaliplatin [XREF_BIBR]."

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"In addition, USP22 knockdown prevented c-MYC-mediated reduction of SIRT1 ubiquitination (XREF_FIG) and increase in SIRT1 expression (XREF_SUPPLEMENTARY)."

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"Collectively, USP22 might deubiquitinate SIRT1 and subsequently activate the AKT pathway, increasing the expression of MRP1 to induce MDR in HCC cells."

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"Ubiquitin specific protease 22 (USP22) reduced Sirt1 ubiquitination and degradation and decreased FN and TGF-beta1 expression in GMCs under both basal and AGEs treated conditions."

trips
"Ubiquitin-specific peptidase USP22 negatively regulates the STAT signaling pathway by deubiquitinating SIRT1."

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"USP22 can deubiquitinate and stabilize the expression of Sirt1."

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"Given that SIRT1 is deubiquitinated by USP22 and stabilized at the protein level (Armour etal., 2013; Lin etal., 2012) and previous studies have reported that SIRT1 could negatively influence the chemosensitivity of HCC cells (Chen etal., 2012), our results supported the notion that USP22 increases SIRT1 protein levels in HCC cells."

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"USP22 can deubiquitinate Sirt1 and enhance its stability through c-MYC-related network, leading to FLT3 tyrosine kinase inhibitors (TKIs) resistance in acute myeloid leukemia (AML)."
USP22 increases the amount of SIRT1.
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USP22 increases the amount of SIRT1. 5 / 5
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"USP22 stabilized and promoted the expression of SIRT1 through its deubiquitination function."

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"Given that SIRT1 is deubiquitinated by USP22 and stabilized at the protein level (Armour etal., 2013; Lin etal., 2012) and previous studies have reported that SIRT1 could negatively influence the chemosensitivity of HCC cells (Chen etal., 2012), our results supported the notion that USP22 increases SIRT1 protein levels in HCC cells."

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"USP22 knockdown reduced SIRT1 expression in FLT3-ITD AML cells, whereas USP22 overexpression increased SIRT1 levels by increasing protein stability, indicating that USP22 is an important positive regulator of SIRT1 in FLT3-ITD cells."

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"USP22 upregulated Sirt1 expression by inhibiting its ubiquitin mediated degradation."

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"In addition, USP22 knockdown prevented c-MYC-mediated reduction of SIRT1 ubiquitination (XREF_FIG) and increase in SIRT1 expression (XREF_SUPPLEMENTARY)."
USP22 activates SIRT1.
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USP22 activates SIRT1. 3 / 4
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"USP22 also increases SIRT1 protein stability, which leads to the suppression of p53 transcriptional activity and inhibition of cell death [XREF_BIBR, XREF_BIBR]."

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"USP22 mediates stabilization of Sirt1 by interacting and removing poly-ubiquitin chains previously conjugated to Sirt1."

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"Simply put, USP22 may activate the SIRT1–AKT–MRP1 pathway and consequently promote MDR in human HCC cells (226)."
USP22 decreases the amount of SIRT1.
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USP22 decreases the amount of SIRT1. 2 / 2
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"In addition, USP22 could also decrease the acetylation of Ku70 by stabilizing the expression of Sirt1, thus inhibiting Bax mediated apoptosis and contributing to cisplatin resistance."

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"Knockdown of endogenous USP22 in MV4-11 cells decreased SIRT1 protein levels (XREF_FIG) and significantly reduced cell growth (XREF_SUPPLEMENTARY)."
Modified USP22 decreases the amount of SIRT1. 1 / 1
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"USP22 knockdown reduced SIRT1 expression in FLT3-ITD AML cells, whereas USP22 overexpression increased SIRT1 levels by increasing protein stability, indicating that USP22 is an important positive regulator of SIRT1 in FLT3-ITD cells."
USP22 ubiquitinates SIRT1.
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USP22 leads to the ubiquitination of SIRT1. 1 / 1
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"USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development."
Modified USP22 leads to the ubiquitination of SIRT1. 1 / 1
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"USP22 overexpression down-regulated STAT3 acetylation by deubiquitinating SIRT1."
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"USP22 Silencing Inhibits Proliferation and Induces Apoptosis and Cell Cycle Arrest in NSCLC Cells."

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"These results suggest that USP22 promotes gastric cancer growth while inhibiting apoptosis in vivo."

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"Silencing of USP22 promotes human retinoblastoma cell apoptosis by inhibiting TERT and P53 pathway 36."

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"In retinoblastoma, the depletion of USP22 has been shown to induce cancer cell apoptosis by suppressing the TERT/P53 signal pathway ."

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"As a consequence, gain of USP22 functions promotes cell cycle progression and inhibits cell apoptosis, leading to cancer cell hyper-proliferation and tumorigenesis."

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"Importantly, overexpression of MDMX reversed USP22 silencing, induced p53 activation, growth inhibition, cell cycle arrest and apoptosis in A549 cells (XREF_FIG B-E)."

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"Previous studies have reported that USP22 gene silencing induced apoptosis of bladder and colorectal cancer cells."

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"RNA interference mediated USP22 gene silencing induced apoptosis of human brain glioma cells."

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"USP22 depletion promotes in vitro GC cell apoptosis."

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"Taken together, these findings strongly indicate that USP22 silencing triggered the mitochondrial apoptosis pathway that is associated with caspase 3 activation in HCC cells."
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"Both elevated exosomal miR-let-7a or silenced USP22 reduced the apoptosis of renal cells and improved kidney function."

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"USP22 depletion could significantly inhibit the proliferation and invasion, and promote the apoptosis of ATC cells in vitro."

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"Further analysis demonstrated that USP22 downregulation activated mitochondrial apoptosis by regulating several apoptosis related proteins, including Bcl-2, Bax, cytochrome c and caspase-3."

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"To investigate the molecular mechanism underlying USP22 silencing induced ATC cell apoptosis, we examined the cellular levels of documented apoptosis regulators or executioners."

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"Additionally, investigation into the underlying mechanism, using small interfering RNA, revealed that the downregulation of USP22 inhibited proliferation and promoted apoptosis though the phosphoinositide 3-kinase/protein kinase B signaling pathway."

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"Silencing of USP22 in podocytes attenuated high d-glucose-induced apoptosis and inflammatory responses, evidenced by increases in proliferation and MMP levels and decreases in the apoptotic rate, ROS production, the Bax and Bcl -2 ratio, caspase-3 expression and secretion of TNF-alpha, IL-1beta, IL-6 and TGF-beta1."

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"Moreover, USP22 down-regulation in HUVECs led to decreased proliferation, angiogenesis, vasodilation, apoptosis, and systolic function."

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"Down-regulation of USP22 expression by siRNA induces the mitochondrial apoptosis of HCC cells."

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"These findings suggest that USP22 accelerates gastric cancer cell proliferation, possibly by suppressing cell apoptosis and promoting the G2/M transition."

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"Our study also shows that USP22 silencing in GC cells decreases cell proliferation and induces cell cycle arrest and apoptosis in vitro, and suppresses tumor growth and metastasis in vivo."
Modified USP22 activates apoptotic process. 1 / 1
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"The overexpression of USP22 significantly enhanced cell proliferation potency and telomerase activity, elevated TERT expression level, inhibited p53 expression and cell aging, as well as decreased cell apoptosis or DNA damage."
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"In lung adenocarcinoma cells, USP22 was implicated to promote cell invasion by the induction of EMT."

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"USP22 and STAT3 co-depletion partly rescued the MMP9 proteolytic activity and invasion of SW480 cells, compared with that of STAT3 depletion alone."

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"USP22 can promote lung cancer cell invasion via epithelial-mesenchymal transition (EMT), which participates in the metastasis of primary tumors by activating TGF-beta1 [XREF_BIBR]."

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"USP22 silencing suppresses in vitro GC cell migration and invasiveness."

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"We drew a conclusion that USP22 could increase the abilities of proliferation, migration and invasion of glioma cells, and promote the growth and development of glioma."

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"Through measuring the proliferation, migration and invasion of SW480 and SW620 cells, we uncovered that USP22 knockdown could suppress the proliferation, migration and invasion of CRC cells, while USP22 overexpression had an opposite effect (Supplement Figure 2)."

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"These results indicate that USP22 increases CRC cell migration and invasion abilities by promoting EMT."

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"Silencing USP22 decreased the migration and invasion of Bel/Fu cells, and combination with 5-Fu further decreased the rate of migration and number of invading cells."

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"Taken together, these results indicate that USP22 increases cell migration and invasion by inducing EMT by binding to the promoter of AP4 to activate its transcription."

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"For example, USP22 mentioned above promotes LUAD cell invasion and migration62."

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"We report that deletion of USP22 in pancreatic tumor cells reduced the infiltration of myeloid cells and promoted the infiltration of T cells and NK cells, leading to an improved response to combination immunotherapy."

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"Ablation of USP22 in liver tumor cells has been shown to increase tumor immunogenicity and promote infiltration of T cells into the resulting liver tumors."
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"USP22 downregulation inhibited OS cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro."

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"In colon cancer, USP22 was reported to attenuate the invasion capacity of colon cancer cells by inhibiting the STAT3 and MMP9 signaling pathway."

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"Downregulation of USP22 inhibited OS cell proliferation, invasion, and EMT in vitro."

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"Downregulation of USP22 inhibited OS cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro."

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"Downregulation of USP22 Inhibited OS Cell Proliferation and Invasion In Vitro."

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"In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3 and MMP9 signaling pathway."

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"The results of in vitro and in vivo studies confirmed USP22 depletion reduced the growth and invasion of ATC cells by regulating the expression and activation of a series of pro tumorigenesis molecules."

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"We also suggested that downregulation of USP22 inhibited OS cell proliferation and invasion in vitro."

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"Downregulation of USP22 reduces in vitro cancer cell proliferation, survival, migration, and invasion, and decreases in vivo tumor growth and metastasis [6, 10–13]."

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"USP22 depletion could significantly inhibit the proliferation and invasion, and promote the apoptosis of ATC cells in vitro."
USP22 affects AR
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USP22 activates AR.
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USP22 activates AR. 10 / 25
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"Given the ability of USP22 to enhance AR accumulation, AR activity, and CRPC, the biological impact of a model of tetracycline inducible shUSP22 was developed in therapy sensitive PCa cells."

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"These data suggest that USP22 functions to enhance AR stability and promote inappropriate castration resistant AR signaling through proteasome dependent regulation of AR levels."

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"Based on the data above, suppression of USP22 in models of ADT sensitive PCa and aggressive CRPC decreased the AR signaling axis (XREF_FIG and XREF_FIG)."

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"By contrast, USP22 deregulation induced marked enhancement of ligand independent AR activity, determined by analyses of multiple, clinically relevant AR target genes (XREF_FIG)."

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"One important distinction is that previous findings are largely based on reporter assays analyzing USP22 mediated AR transactivation in Drosophila and human embryonic kidney (HEK) cells, and AR expression perturbation under conditions of ectopic overexpression of AR and USP22 in HEK cells."

eidos
"USP22 modulates both AR and MYC activity [ 8] , and USP22 mRNA expression was positively correlated with both AR and MYC mRNA expression ( p = 7.76e-14 and p =3 .36 e-7 , respectively ; Figure 1B ) , further supporting a pro-oncogenic role for USP22 in tumors with elevated AR and MYC expression ."

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"USP22, ATXN7L3, and ENY2 significantly enhanced AR mediated transactivation in the presence of ligand (2.5- to 3.5-fold compared to AR alone), similarly to the effect of the GCN5 HAT."

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"Together, these data demonstrate that USP22 regulates ligand independent AR residence at target gene loci and promotes AR driven CRPC gene profiles, which may have specificity for USP22 perturbation, further implicating USP22 as an independent effector of aggressive tumor phenotypes."

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"These data demonstrate that USP22 potentiates both ligand dependent and ligand independent AR function."

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"In addition, USP22 expression was shown to increase the abundance of c-Myc and the androgen receptor itself [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
USP22 binds AR.
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"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"No significant association of AR and USP22 with chromatin at an intergenic region could be detected, and the amount of histone H3 at KLK2 promoter remained constant, further demonstrating specificit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Subsequent immunoprecipitation also confirmed the association between AR and USP22 in vitro, which is consistent with the result of previous studies (Fig. 3I)."

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"Cotransfection in HEK293T cells and coimmunoprecipitation experiments revealed that AR interacted with ATXN7L3 in a ligand dependent manner, similarly to GCN5, while interaction between AR and USP22 w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Cotransfection in HEK293T cells and coimmunoprecipitation experiments revealed that AR interacted with ATXN7L3 in a ligand-dependent manner, similarly to GCN5, while interaction between AR and USP22 w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As AR and USP22 interacted in vivo, we next tested whether AR could be a substrate of the TFTC/STAGA deubiquitination activity."
USP22 binds ATXN7L3 and AR. 2 / 2
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sparser
"To further investigate this hypothesis, we analyzed putative interactions of USP22 or ATXN7L3 with AR in mammalian cells."

sparser
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR-dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 inhibits AR.
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USP22 inhibits AR. 4 / 6
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"In androgen deprived conditions, USP22 depletion modestly decreased basal AR activity."

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"As shown, in CRPC cells, USP22 depletion suppressed AR protein accumulation in both the androgen stimulated and deprived conditions (XREF_FIG, compare lanes 1,2 and 3,4)."

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"First, depletion of USP22 significantly reduced AR protein (~ 73%) compared to control (XREF_FIG, compare lanes 3,4 and 7,8)."

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"Additionally, in both culture conditions, USP22 depletion diminished AR activity (XREF_FIG)."
USP22 decreases the amount of AR.
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USP22 decreases the amount of AR. 4 / 5
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"USP22 Depletion Suppresses Ligand Dependent and Castration Resistant AR Expression and Activity."

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"Schrecengost et al XREF_BIBR previously showed that USP22 depletion dramatically downregulated androgen receptor protein levels and abolished androgen receptor activity in both androgen deprivation therapy and castration resistant prostate adenocarcinoma cells."

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"Conversely, depletion of USP22 dramatically down-regulates AR protein levels and abrogates basal and DHT stimulated AR activity in both ADT sensitive and CRPC cells."

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"In contrast, USP22 depletion reduced AR protein levels in the absence of androgen, and inhibited DHT induced AR expression, within in models of therapy sensitive disease (XREF_FIG, compare lanes 2, 4)."
USP22 increases the amount of AR.
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USP22 increases the amount of AR. 3 / 4
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"The observations that USP22 upregulation is sufficient to promote ligand independent AR expression and activity, and induce Casodex resistance are clinically relevant, as these attributes reflect key biochemical characteristics of CRPC."

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"And correspondingly, overexpression of USP22 stabilized AR-V7 expression in a manner similar to USP14 (Fig. 5A–D), demonstrating that USP22 may also be involved in stabilizing the protein level of AR-V7, similar to USP14.In fact, the regulation of AR expression and function by USP22 in prostate cancer has been reported [37], but whether AR-V7 could be regulated by USP22 is elusive."

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"Further, USP22 mediates AR expression through a proteasome dependent mechanism, since modeling clinically-relevant USP22 upregulation results in an increased AR protein half-life and proteasome inhibition rescued the decreased AR expression following USP22 depletion."
USP22 affects BMI1
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USP22 binds BMI1.
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sparser
"It is noteworthy that RNF220 regulates BMI1 expression via USP22, therefore, USP22-BMI1 axis was validated in this study to function in colorectal cancer progression."

sparser
"Ring finger 220 promotes the stemness and progression of colon cancer cells via Ubiquitin specific peptidase 22-BMI1 axis."

sparser
"USP22-BMI1 axis are reported to be involved in the stemness of many types of cancer cells."

sparser
"In conclusion, RNF220 promoted the stemness and progression of colon cancer cells via the USP22-BMI1 axis."

sparser
"Overexpression of USP22 and BMI1 was previously associated with GC progression and therapy failure through clinical specimen analysis, and our study is consistent with these results."

sparser
"Hypoxia-induced USP22-BMI1 axis accelerates the malignancy and stemness of glioma stem cells by regulating the HIF-1α [ xref ]."

sparser
"Moreover, we found that high USP22 expression was often associated with high BMI1 expression in HCC patients."

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"To examine whether USP22 can interact with BMI1, we coexpressed exogenous GFP-BMI1 with either the wild-type or catalytic inactive (C185S) mutant USP22 in HEK293FT cells."

sparser
"In this study, we discovered that RNF220 level was elevated in colorectal cancer, promoting the migration, invasion and proliferation of colorectal cancer cells through USP22-BMI1 axis."

sparser
"USP22, and BMI1 form a polyprotein complex that acts on its target homoeotic (Hox) gene cluster."
USP22 increases the amount of BMI1.
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USP22 increases the amount of BMI1. 6 / 6
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"Our results showed that USP22 silencing significantly down-regulated BMI1 protein expression and further affected gastric CSC self-renewal."

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"USP22 knockdown remarkably decreased BMI1 protein level, but it barely affected BMI1 mRNA level in glioma cell lines."

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"Above, we demonstrated that USP22 silencing predominantly decreases the BMI1 protein levels rather than mRNA expression, and further alters GC cell proliferation, gastric CSC formation and maintenance of stem cell stemness, indicating post-transcriptional regulation of BMI1."

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"We found USP22 silencing led to decreased expression of BMI1, as well as decreased P21 levels."

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"We have reported that USP22 mediates cell survival and proliferation by promoting the expression of BMI-1 and upregulation of activated AKT pathway in colon cancer cells."

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"USP22 knockdown inhibits glioma stemness partially by downregulating the protein level but not the transcriptional level of BMI1."
USP22 activates BMI1.
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USP22 activates BMI1. 6 / 6
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"Moreover, WT-USP22 prolonged GFP-BMI1 half-life compared with that in cells transfected with control vector or CI-USP22."

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"In this study, we demonstrated that USP22 mediated protein stabilization of BMI1 promotes gastric CSC stemness maintenance and GC progression, thereby providing a rationale for USP22 targeting as a potential therapeutic approach against GC."

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"Additionally, USP22 silencing led to down-regulated BMI1."

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"Previous studies have confirmed that USP22 can promote the biological process of NSCLC cells by regulating BMI-1 and AKT signaling pathway [XREF_BIBR]."

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"USP22 maintains gastric cancer stem cell stemness and promotes gastric cancer progression by stabilizing BMI1 protein."

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"An in vitro study showed that the upregulation of USP22 mediated the enhanced expression of BMI1 and Cyclin D2, and was responsible for increased cell proliferation and the metastatic behavior of colon cancer cells ."
USP22 deubiquitinates BMI1.
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USP22 deubiquitinates BMI1. 4 / 4
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"All these findings indicate USP22 as a novel deubiquitinase of BMI1 in glioma."

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"3.3 USP22 deubiquitinates BMI1 for protein stabilization."

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"USP22 interacts with and deubiquitinates BMI1 for post-translational stabilization."

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"To test whether the endogenous BMI1 is also deubiquitinated by USP22 in glioma cells, we knocked down endogenous USP22 in U251 cells pretreated with CHX and found that endogenous BMI1 also became unstable and degraded rapidly."
Modified USP22 leads to the deubiquitination of BMI1. 1 / 1
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"However, WT-USP22 coexpression (not CI-USP22) almost completely abolished BMI1 ubiquitination (lane 2 vs lane 3, Figure XREF_FIG B)."
USP22 decreases the amount of BMI1.
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USP22 decreases the amount of BMI1. 1 / 1
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"In this study, we showed that USP22 depletion significantly decreased the expressions of BMI-1, vimentin, and snail and increased E-cadherin expression in ATC cells."
USP22 is modified
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USP22 is phosphorylated.
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USP22 is phosphorylated. 10 / 25
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rlimsp
"In contrast, the degradation of CCNB1 was blocked in HCT116-USP22/DD cells, suggesting that CDK1-mediated USP22 phosphorylation enhances its ability to stabilize CCNB1 (Figure 4f) and may be involved in mitotic progression (Supplementary Figure S4f)."

sparser
"These findings show that CDK1 is a kinase that catalyzes USP22 phosphorylation in a cell cycle-specific manner."

sparser
"In an in vitro kinase assay, co-incubation of the purified GST-USP22 fusion proteins and the constitutive forms of CDK1 (CDK1/AF) immunoprecipitated from transiently transfected HCT116 cells confirmed USP22 phosphorylation by CDK1 ( xref )."

sparser
"Interestingly, USP22 activity is regulated by CDK1, which catalyzes USP22 phosphorylation to elevate USP22 ability in CCNB1 deubiquitination and stabilization."

rlimsp
"Interestingly, USP22 activity is regulated by CDK1, which catalyzes USP22 phosphorylation to elevate USP22 ability in CCNB1 deubiquitination and stabilization."

sparser
"To test our hypothesis, we purified USP22 protein from HCT116 cells, treated the protein with calf intestinal alkaline phosphatase, which presumably suppresses USP22 phosphorylation, and then co-incubated it with ubiquitinated CCNB1 protein."

rlimsp
"After 24 h, cells were treated without or with nocodazole for 12 h. USP22 phosphorylation in the lysates of transfected cells was analyzed."

rlimsp
"USP22 phosphorylation in the lysates of treated cells was analyzed as described in b. (d) Conserved T147 and S237 amino acids of USP22 in each indicated species are shown."

sparser
"Moreover, cyclin B1-Cdk1 leads to USP22 phosphorylation on residues Thr147 and Ser237, which in turns promotes its deubiquitinase activity."

rlimsp
"In addition, expression of the constitutively active form of CDK1 (CDK1/AF) [37, 38] further enhanced USP22 phosphorylation in HCT116 cells (Figure 4b)."
USP22 is phosphorylated on S237. 4 / 4
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No evidence text available

rlimsp
"In addition, in vitro kinase assays confirmed that T147 and S237 are the phosphorylation sites of USP22 because co-incubation with the constitutively active form of CDK1 failed to induce USP22/AA phosphorylation (Supplementary Figure S4d)."

rlimsp
"Replacing both T147 and S237 with alanine (AA) completely abolished USP22 phosphorylation and led to decreased CCNB1 protein levels even when CDK1 was co-expressed in HCT116 cells (Figure 4e and Supplementary Figure S4e)."

rlimsp
"Proteomic analysis of the USP22 proteins from cells expressing the constitutively active forms of CDK1 identified two phosphorylated amino acids of USP22, S237 and T147 (Supplementary Figure S4a and S4b), both of which are conserved amino acids from Xenopus to human (Figure 4d)."
USP22 is acetylated.
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USP22 is acetylated. 4 / 4
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sparser
"Furthermore, our data suggest that ATAC and SAGA control of gene transcription may be more specific than control of promoter H3K9 acetylation, indicating that specificity of transcriptional regulation by either complex may rely on unique effects of their additional enzymatic activities, namely H2B deubiquitination by USP22 and H4 acetylation by KAT14. xref Accordingly, our inspection of USP22 requirements in erythropoiesis suggest that they align with the stage specificity of SAGA but may exceed the effects of loss of SUPT20H and more directly resemble postcommitment contributions of KAT2A . Future studies investigating single and combined requirements of ATAC and SAGA enzymatic subunits in locus and cellular regulation will enhance our understanding of the transcriptional control of cell state and fate decisions, including in leukemia and the normal blood system."

sparser
"USP22 is acetylated [ xref ], and USP7 is phosphorylated [ xref ]."

sparser
"Interestingly, SIRT1 was identified as a mediator of acetylation of USP22 and the SAGA coactivator complex (Armour et al ., xref )."

sparser
"Interestingly, SIRT1 was also identified as a mediator of acetylation of USP22 and the SAGA coactivator complex [ xref ]."
USP22 is acetylated on K129. 2 / 2
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sparser
"Acetylation of USP22 on lysine 129 (K129) regulates USP22 deubiquitylase activity and its association with the SAGA complex."

No evidence text available
USP22 is ubiquitinated.
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USP22 is ubiquitinated. 5 / 5
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sparser
"Lastly, ubiquitylation of USP22 mediated by the anaphase promoter complex/cyclosome (APC/C) induces USP22 protein degradation during the cell cycle [ xref ]."

sparser
"Among these differentially ubiquitylated USP22 targets numerous DNA repair proteins, including XPC and RAD23B, were identified."

sparser
"However, of those four DUBs, only USP22 substantially decreased KDM1A ubiquitination ( xref )."

sparser
"Fourth, USP22 is ubiquitinated and degraded by CDC20-containing APC/C complex during cell exit from M phase, presumably to release the brake on CCNB1 degradation."

sparser
"Besides, USP22 could remove poly-ubiquitin chain of CSN5, while CSN5 seemed no effect on USP22 ubiquitination (Fig. xref c, Fig. xref d)."
USP22 is deubiquitinated.
| 2
USP22 is deubiquitinated. 2 / 2
| 2

trips
"Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma."

trips
"Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells."
USP22 affects cell cycle
| 3 37
USP22 activates cell cycle.
| 3 22
| 3 22

eidos
"Therefore , up-regulation of USP22 expression will lead to abnormal activation of multiple pathways to promote cell survival while down-regulation of USP22 expression can induce cell cycle arrest at G0 / G1 phase in different types of cancer cells ( Zhang et al ., 2008 ) ."

reach
"We found that inhibition of USP22 suppressed cell proliferation by inducing G1 phase cell cycle arrest through synergy with oncogenic transforming growth factor-beta1 (TGFB1)."

reach
"Therefore, reduced USP22 expression can not systematically induce cell cycle arrest and hinder cancer progression, as suggested above."

reach
"XREF_BIBR In addition, another study demonstrated that silencing USP22 could inhibit proliferation and induce cell cycle arrest in bladder cancer cells."

reach
"USP22 Modulates Cell Cycle Progression."

reach
"First, using hormone-proficient conditions, USP22 enhanced the rate of cell cycle progression, evidenced through increased BrdU incorporation (XREF_FIG, left)."

reach
"Moreover, USP22 promotes cell cycle progression by regulating BMI-mediated INK4a/ARF and Akt signaling pathways [12, 32–34]."

reach
"USP22 regulates CCNB1 protein stability to promote cell cycle progression, as well as cancer cell growth, when it is aberrantly upregulated."

reach
"Nevertheless, significant evidence is accumulating that indicates USP22 expression promotes cell cycle progression in certain cancer cell lines and that USP22 overexpression may enhance proliferation of cancer cells by facilitating premature transition through various cell cycle stages."

reach
"As CCNB1 regulates cell cycle progression by interacting with and activating CDK1 [XREF_BIBR], we asked whether USP22, which has been shown to promote cell cycle progression [XREF_BIBR], regulates CDK1 activation through CCNB1 stabilization."
USP22 inhibits cell cycle.
| 15
| 15

reach
"Importantly, overexpression of MDMX reversed USP22 silencing, induced p53 activation, growth inhibition, cell cycle arrest and apoptosis in A549 cells (XREF_FIG B-E)."

reach
"As shown, doxycycline (Dox) decreased USP22, resulting in marked loss of AR (XREF_FIG, top), attenuated cell cycle progression (determined by BrdU incorporation XREF_FIG, top right, middle), and significantly suppressed of cell doubling (XREF_FIG, bottom)."

reach
"Also, USP22 silencing promotes apoptosis and cell cycle arrest in human brain gliomas."

reach
"RNA interference mediated USP22 gene silencing promotes human brain glioma apoptosis and induces cell cycle arrest."

reach
"XREF_BIBR - XREF_BIBR Zhang and colleagues have demonstrated that ectopic overexpression of USP22 promotes cell proliferation and that suppression of USP22 expression by small hairpin RNA induces cell cycle arrest in human lung cancer cells."

reach
"Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others."

reach
"USP22 Silencing Inhibits Proliferation and Induces Apoptosis and Cell Cycle Arrest in NSCLC Cells."

reach
"Meanwhile, our flow cytometry analysis revealed that, compared with the control, USP22 shRNA transfected cells displayed a significantly higher portion of cells at the G0/G1 phases and significantly lower portions of cells at the S and G2/M phases (XREF_FIG C), indicating that USP22 silencing induces cell cycle arrest."

reach
"Silencing USP22 by asymmetric structure of interfering RNA inhibits proliferation and induces cell cycle arrest in bladder cancer cells."

reach
"Our group first ensured that knockdown of USP22 can induce cell cycle arrest and inhibit cell growth in the HCC cell line HepG2 (Ling etal., 2012a)."
| 3 36
| 3 26

reach
"These data demonstrate that USP22 promotes in vivo GC growth and metastasis."

reach
"USP22 may promote tumor progression and metastasis."

reach
"We found that the USP22 expression increased significantly from normal mucosa to carcinomas and from carcinomas to lymph node metastasis."

eidos
"As expected , downregulation of USP22 suppressed OS tumor growth and metastasis in vivo ."

reach
"USP22 stimulates CRC cell metastasis in vivo."

reach
"The USP22 increases growth and metastasis of HCC cells via inducing Wnt/β-catenin signaling."

reach
"Moreover, USP22 and AP4 overexpression may stimulate tumor metastasis and adversely affect OS in CRC patients."

eidos
"These results suggest that USP22 downregulation inhibited OS tumor growth and metastasis in vivo ."

reach
"In vivo, elevated USP22 expression promotes CRC cell metastasis to the lungs in nude mice, as evidenced by the fact that CRC metastatic nodules stain deeply positive for USP22 and AP4."

reach
"Here, we propose a novel mechanism by which USP22 drives CRC progression and metastasis."
| 10

reach
"Consistent with in vitro findings, downregulation of USP22 in ATC cells impeded tumor growth and lung metastasis in vivo."

reach
"Moreover, USP22 overexpression can promote EMT and TGF-beta expression, whereas depletion of USP22 can reverse EMT and reduce metastasis of lung adenocarcinomas."

reach
"XREF_BIBR Downregulation of USP22 has been shown to suppress osteosarcoma growth and metastasis through PI3K and Akt pathway."

reach
"Downregulation of USP22 Inhibited OS Tumor Growth and Metastasis In Vivo."

reach
"In addition, downregulation of USP22 suppressed OS tumor growth and metastasis in vivo."

reach
"Similarly, Zhao et al. reported that USP22 depletion suppressed cell survival and proliferation as well as tumor growth and lung metastasis of anaplastic thyroid carcinoma cells XREF_BIBR."

reach
"As expected, downregulation of USP22 suppressed OS tumor growth and metastasis in vivo."

reach
"We also showed that ablation of tumor cell-intrinsic USP22 suppressed metastasis of pancreatic tumor cells in a T cell dependent manner."

reach
"These results suggest that USP22 downregulation inhibited OS tumor growth and metastasis in vivo."

reach
"Collectively, these results suggested that USP22 depletion attenuates tumor growth and metastasis of ATC."
CDK1 affects USP22
1 | 10 12 11
CDK1 phosphorylates USP22.
| 8 11 11
CDK1 phosphorylates USP22. 10 / 26
| 8 7 10

rlimsp
"Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1."

rlimsp
"CDK1 phosphorylates USP22 to optimize its activity in CCNB1 stabilization during the G2/M phase."

sparser
"We then analyzed whether USP22 is phosphorylated by CDK1."

rlimsp
"From our proteomic analysis, we noticed that CCNB1 appears to form a complex with both USP22 and CDK1; this prompted us to ask whether CDK1 phosphorylates USP22."

reach
"Third, USP22 is phosphorylated by CDK1 during the G2/M phase of the cell cycle and this phosphorylation optimizes the enzyme activity of USP22 to deubiquitinate CCNB1."

reach
"CDK1 phosphorylates USP22 to optimize its activity in CCNB1 stabilization during the G2/M phase."

sparser
"CDK1 phosphorylates USP22 to enhance its activity in CCNB1 stabilization during G2/M phase."

reach
"In addition, expression of the constitutively active form of CDK1 (CDK1/AF) [XREF_BIBR, XREF_BIBR] further enhanced USP22 phosphorylation in HCT116 cells (XREF_FIG)."

sparser
"Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1."

rlimsp
"These findings show that CDK1 is a kinase that catalyzes USP22 phosphorylation in a cell cycle-specific manner."
CDK1 phosphorylates USP22 on S237. 3 / 3
| 2 1

sparser
"Phosphorylation of USP22 at T147 and S237 by CDK1 increases the deubiquitination status of cyclin B1 in a cell cycle dependent manner."

sparser
"Phosphorylation of USP22 at T147 and S237 by cyclin-dependent kinase 1 (CDK1) was shown to activate USP22 to deubiquitylate cyclin B1."

rlimsp
"These results indicate that T147 and S237 are the potential CDK1 phosphorylation sites and imply that these residues have important functions in CDK1-mediated USP22 phosphorylation."
CDK1 phosphorylates USP22 on T147. 2 / 2
| 2

sparser
"Phosphorylation of USP22 at T147 and S237 by cyclin-dependent kinase 1 (CDK1) was shown to activate USP22 to deubiquitylate cyclin B1."

sparser
"Phosphorylation of USP22 at T147 and S237 by CDK1 increases the deubiquitination status of cyclin B1 in a cell cycle dependent manner."
CDK1 activates USP22.
| 2
CDK1 activates USP22. 2 / 3
| 2

reach
"USP22 is activated by CDK1 phosphorylation and deubiquitinates and stabilizes Cyclin B1 to promote cell cycle progression [XREF_BIBR]."

reach
"On the other hand, CDK1 enhances USP22 activity to stabilize CCNB1 during the G2/M phase."
CDK1 binds USP22.
1 | 1
1 | 1

No evidence text available

sparser
"From our proteomic analysis, we noticed that CCNB1 appears to form a complex with both USP22 and CDK1; this prompted us to ask whether CDK1 phosphorylates USP22."
SIRT1 affects USP22
10 | 9 14
SIRT1 binds USP22.
10 | 8 14
10 | 8 13

reach
"Our studies suggest that SIRT1 and CCNB1 interact with USP22 through different regions."

sparser
"In this study, USP22 directly interacted with SIRT1 and positively regulated SIRT1 protein expression."

sparser
"These findings suggest that the co-expression of USP22 and SIRT1 is significantly associated with unfavorable HCC progression."

reach
"USP22 can also form a complex with the histone deacetylase SIRT1, which serves a similar repressive action on Sox2."

sparser
"Additionally, to better understand the role of USP22-SIRT1 axis in ferroptosis-induced cell death, the effects of overexpression or knockdown of SIRT1 on ferroptosis signaling pathway were examined using Western blot analysis ( xref )."

reach
"USP22 directly interacts with SIRT1 based on the co-immunoprecipitation assay."

sparser
"In our previous study, USP22 bound to SIRT1 and subsequently activated the AKT pathway, increasing the expression of MRP1 to induce 5-FU resistance in HCC cells [ xref ]."

sparser
"SIRT1 physically interacts with USP22 as a mediator of USP22."

reach
"These results indicate that USP22 directly interacts with SIRT1 and contributes to stabilization of SIRT1 protein in FLT3-ITD AML cells."

sparser
"USP22 Interacts with SIRT1 and Maintains Its Protein Expression."
USP22 binds SIRT1 and FLT3. 1 / 1
| 1

sparser
"We show that USP22 directly interacts with SIRT1 in FLT3-ITD AML cells in a FLT3-kinase-independent manner."
SIRT1 inhibits USP22.
| 1
SIRT1 inhibits USP22. 1 / 1
| 1

reach
"Mechanistically, KLF3-AS1 inhibited the ubiquitination of Sirt1 protein through inducing USP22."
USP22 affects MYC
4 1 | 19 5
USP22 activates MYC.
| 13
USP22 activates MYC. 10 / 16
| 13

reach
"Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity."

reach
"While these outcomes could occur via USP22 mediated MYC and CyclinD2 and/or BMI-1-mediated modulation, AR activity promotes tumorigenesis in several of these tumor types, including bladder, HCC and breast carcinoma."

reach
"USP22 depletion in the lung cancer cells decreases the transcriptional ability of Myc [4]."

reach
"In this study, we found that USP22 overexpression induces c-myc upregulation in both SGC7901 cells and tumor tissue, consistent with previous reports."

reach
"Evidently, HnRNPA1 is a downstream transcription regulator of c-Myc (proto-oncogene) whereas USP22 positively regulates c-Myc stability and promotes tumorigenesis [XREF_BIBR, XREF_BIBR]."

reach
"C-Myc abundance is also indirectly increased by the activity of USP22 on its substrate SIRT1, a NAD dependent protein deacetylase [XREF_BIBR] (see Section 7), but this is not observed in all cell types [XREF_BIBR]."

reach
"Decreased levels of USP22 reduce the ability of c-MYC, which can stimulate activation of AP4 to directly or indirectly induce EMT [XREF_BIBR], activating the transcription of its targets [XREF_BIBR, XREF_BIBR]."

reach
"USP22 increases the stability and tumorigenic activity of c-Myc in breast cancer cells [30]."

reach
"In addition, USP22 expression was shown to increase the abundance of c-Myc and the androgen receptor itself [XREF_BIBR, XREF_BIBR, XREF_BIBR]."

reach
"Studies herein suggest that USP22 mediated MYC regulation in PCa is likely gene selective, based on USP22 increasing gene expression of AR/MYC co-regulated target (ODC) but not of multiple MYC targets."
USP22 binds MYC.
4 | 1 5
4 | 1 5

sparser
"It has been reported that SIRT1 protein level is increased in LSCs in both chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), by either transcriptional induction in CML or by c-Myc-USP22 mediated stabilization of SIRT1 protein in AML [ xref ]."

sparser
"In addition, it has been shown that USP22 interacts with the c-Myc transcription factor in cancer cells ( xref ), and genetic c-Myc suppression impairs iNKT development but with increased PLZF expression ( xref ; xref ), raising the possibility that USP22 represses PLZF expression through its interaction with c-Myc."

No evidence text available

reach
"The data presented here suggest that the recruitment of USP22 to Myc targets as part of the hSAGA complex may provide this critical function.An outstanding question raised by these studies is the iden[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

No evidence text available

sparser
"However, ChIP analysis failed detect USP22 binding to PLZF promoter DNA, together with the fact that USP22 interaction with c-Myc enhances but not suppresses c-Myc transcriptional activity ( xref ), largely excluding the possibility that USP22 inhibits PLZF transcription through c-Myc."

No evidence text available

sparser
"These results support a role for USP22 in MYC-mediated increase in SIRT1 protein stabilization, and indicate that FLT3-ITD, c-MYC and USP22 form an oncogenic network that enhances SIRT1 expression and activity in leukemic cells."

sparser
"Mechanically, USP22 interacted with c-Myc to promote its stabilization by deubiquitination in TNBC cells."
USP22 deubiquitinates MYC.
1 | 2
USP22 deubiquitinates MYC. 3 / 3
1 | 2

reach
"It could be through a direct mechanism where USP22 deubiquitylates c-MYC inducing its stabilization and activation, or indirectly through ubiquitin removal from histones at c-MYC target genes, recruitment of other transcriptional machinery or deubiquitylation of proteins important for c-MYC activity."

reach
"We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc."
USP22 increases the amount of MYC.
| 2
USP22 increases the amount of MYC. 2 / 2
| 2

reach
"Levels of MYC, a critical transcription factor driver in many cancers, are enhanced by USP22 (REF."

reach
"These data suggest that USP22 promotes GC progression.USP22 and c-Myc are co-expressed in GC tissues [7]."
USP22 inhibits MYC.
| 1
USP22 inhibits MYC. 1 / 1
| 1

reach
"Because the Myc protein controls the expression of thousands of other genes, the depletion of cellular USP22 can inhibit Myc function, inhibiting the invasive growth of cancer cells."
USP22 affects CCNB1
4 1 | 16 7
USP22 binds CCNB1.
4 | 5 7
4 | 5 7

reach
"USP22 binding to Cyclin B1, promotes cyclin B1 accumulation in the nucleus and inhibits its degradation [XREF_BIBR]."

sparser
"To further refine our understanding of the molecular interaction between USP22 and CCNB1, we generated truncated USP22 mutants ( xref )."

No evidence text available

sparser
"However, this report clearly demonstrates that USP22 binds and deubiquitinates cyclin B1, leading to its stabilization."

No evidence text available

sparser
"The interaction between endogenous USP22 and CCNB1 in human colon cancer cells was also detected, as anti-CCNB1-specific antibody but not normal mouse immunoglobulin G immunoprecipitated USP22 protein ( xref )."

sparser
"In addition, as S237 is also within the portion of USP22 that interacts with CCNB1, it is possible that CDK1-mediated S237 phosphorylation enhances USP22 interaction with CCNB1."

sparser
"USP22 interacts with CCNB1."

No evidence text available

sparser
"USP22 binding to Cyclin B1, promotes cyclin B1 accumulation in the nucleus and inhibits its degradation [ xref ]."
USP22 activates CCNB1.
| 8
USP22 activates CCNB1. 7 / 9
| 7

reach
"USP22 mediated CCNB1 stabilization is regulated by both CDK1 and the APC/C E3 ubiquitin ligase complex."

reach
"Given that degradation of CCNB1 is required for cells to exit M phase and enter anaphase [XREF_BIBR, XREF_BIBR], we proposed that USP22 degradation, which presumably allows CCNB1 degradation during late M phase, is necessary for cell cycle regulation."

reach
"Our discovery here, that both USP22 and CCNB1 proteins are elevated and positively associated in human colon cancers, indicates that USP22 mediated CCNB1 stabilization is one possible molecular mechanism underlying its proto-oncogenicity."

reach
"Therefore, APC and CDC20 E3 ligase complex promotes USP22 protein degradation, presumably allowing CCNB1 degradation for cells to exit M phase."

reach
"In addition, Usp22 promotes CRC by stabilizing cyclin B1."

reach
"Phosphorylation of USP22 at T147 and S237 by CDK1 increases the deubiquitination status of cyclin B1 in a cell cycle dependent manner."

reach
"Moreover, the proteasome inhibitor MG132 protected CCNB1 from degradation in usp22 knockdown cells (XREF_FIG), implying that USP22 mediates CCNB1 stabilization through regulating the proteasomal pathway."
USP22 bound to CCNB1 activates CCNB1. 1 / 1
| 1

reach
"USP22 binding to Cyclin B1, promotes cyclin B1 accumulation in the nucleus and inhibits its degradation [XREF_BIBR]."
USP22 deubiquitinates CCNB1.
1 | 3
USP22 deubiquitinates CCNB1. 4 / 4
1 | 3

reach
"USP22 deubiquitinates cyclin B1, stabilizes cyclin B1 by antagonizing proteasome mediated degradation, and promotes itaccumulation in the nucleus (Lin etal., 2015; Melo-Cardenas etal., 2016)."

"Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1."

reach
"Indeed, USP22 inhibited CCNB1 ubiquitination both in vivo and in vitro (XREF_FIG and XREF_SUPPLEMENTARY)."

reach
"The deubiquitinase catalytic activity of USP22 is required for CCNB1 deubiquitination because the catalytically inactive USP22 (USP22 and C185A) mutant failed to suppress CCNB1 ubiquitination without affecting its interaction with CCNB1 (XREF_SUPPLEMENTARY)."
BMI1 affects USP22
| 8 22
BMI1 binds USP22.
| 5 22
| 5 22

sparser
"It is noteworthy that RNF220 regulates BMI1 expression via USP22, therefore, USP22-BMI1 axis was validated in this study to function in colorectal cancer progression."

sparser
"Ring finger 220 promotes the stemness and progression of colon cancer cells via Ubiquitin specific peptidase 22-BMI1 axis."

sparser
"USP22-BMI1 axis are reported to be involved in the stemness of many types of cancer cells."

sparser
"In conclusion, RNF220 promoted the stemness and progression of colon cancer cells via the USP22-BMI1 axis."

sparser
"Overexpression of USP22 and BMI1 was previously associated with GC progression and therapy failure through clinical specimen analysis, and our study is consistent with these results."

sparser
"Hypoxia-induced USP22-BMI1 axis accelerates the malignancy and stemness of glioma stem cells by regulating the HIF-1α [ xref ]."

sparser
"Moreover, we found that high USP22 expression was often associated with high BMI1 expression in HCC patients."

reach
"To examine whether USP22 can interact with BMI1, we coexpressed exogenous GFP-BMI1 with either the wild-type or catalytic inactive (C185S) mutant USP22 in HEK293FT cells."

sparser
"In this study, we discovered that RNF220 level was elevated in colorectal cancer, promoting the migration, invasion and proliferation of colorectal cancer cells through USP22-BMI1 axis."

sparser
"USP22, and BMI1 form a polyprotein complex that acts on its target homoeotic (Hox) gene cluster."
BMI1 activates USP22.
| 2
BMI1 activates USP22. 2 / 2
| 2

reach
"These results showed that BMI1 mediates the effect of USP22 on glioma stemness."

reach
"Considering BMI1 is a potential target of USP22 in other cancers,21, 22 we attempted to examine whether BMI1 may mediate the effect of USP22 on glioma stemness."
BMI1 inhibits USP22.
| 1
BMI1 inhibits USP22. 1 / 1
| 1

reach
"BMI1 abrogates the inhibitory effect of USP22 knockdown on CSC formation."

reach
"These results suggested that overexpression USP22 induced EMT in lung adenocarcinoma cells.Moreover it is well known that TGF-beta1 stimulates the EMT in lung cancer cells [43]."

eidos
"Previous studies have also shown that USP22 can promote tumor progression and induce EMT in various tumors [ 13 , 23 ] ."

eidos
"A more recently published report indicates that USP22 may promote tumor progression and induce EMT in colorectal carcinoma patients [ 13 ] ."

reach
"These findings indicate that USP22 promotes CRC invasion and metastasis by inducing EMT via AP4 activation."

reach
"USP22 increases CRC cell migration and invasion by inducing EMT."

reach
"According to the results of previous studies, USP22 can induce EMT by regulating TGF-beta1 in lung cancer cells [XREF_BIBR], and elevated USP22 expression can promote EMT by up-regulating ZEB1 and Snail in pancreatic cancer cells though a process that involves focal adhesion kinase (FAK) signaling [XREF_BIBR]."

reach
"In vitro study revealed that USP22 can regulate proliferation and invasive properties, and induce EMT of lung adenocarcinoma cells."

reach
"In vitro, USP22 overexpression promoted the EMT process of NRK-52E cells stimulated by HG and further increased the levels of extracellular matrix (ECM) components such as fibronectin, Collagen I, and Collagen Ⅳ."

reach
"These results suggested that overexpression USP22 may cause EMT in lung adenocarcinoma cells."

reach
"USP22 overexpression enhanced the extracellular acidification rate, proliferation, spheroid number, CD44+/CD24- cell number, and the expression of stemness genes and EMT-related markers in TNBC/DDP cells, while these effects were restrained by glycolysis inhibitors."

reach
"Moreover, USP22 overexpression can promote EMT and TGF-beta expression, whereas depletion of USP22 can reverse EMT and reduce metastasis of lung adenocarcinomas."

reach
"Downregulation of USP22 inhibited OS cell proliferation, invasion, and EMT in vitro."

reach
"The results suggested that USP22 downregulation obviously suppressed the EMT process in OS cells."
USP22 affects KDM1A
1 | 21 3
USP22 binds KDM1A.
| 4 3
| 4 3

sparser
"Using a series of KDM1A deletion mutants, we found that KDM1A’s AOL domain was required for KDM1A’s binding with USP22 ( xref )."

reach
"Moreover, GSK3beta knockdown in GSC11 cells attenuated the interaction between endogenous USP22 and KDM1A (XREF_FIG), which was confirmed in 293T cells by transfection of GSK3beta-KD as compared with GSK3beta-CA (XREF_SUPPLEMENTARY)."

reach
"The target relationship of USP22 and miR-362-3p as well as the interaction of USP22 and LSD1 in RB was verified."

sparser
"The target relationship of USP22 and miR-362-3p as well as the interaction of USP22 and LSD1 in RB was verified."

sparser
"Moreover, GSK3β knockdown in GSC11 cells attenuated the interaction between endogenous USP22 and KDM1A ( xref ), which was confirmed in 293T cells by transfection of GSK3β-KD as compared with GSK3β-CA ( xref )."

reach
"Using a series of KDM1A deletion mutants, we found that KDM1A 's AOL domain was required for KDM1A 's binding with USP22 (XREF_FIG)."

reach
"Furthermore, KDM1A S683A significantly decreased the interaction between USP22 and KDM1A in the presence of GSK3beta-CA (XREF_FIG)."
USP22 deubiquitinates KDM1A.
1 | 7
USP22 deubiquitinates KDM1A. 8 / 8
1 | 7

reach
"These results indicate that USP22 deubiquitinates and stabilizes KDM1A."

reach
"Moreover, using in vitro deubiquitination assay, we found that KDM1A ubiquitination was decreased by incubating with recombinant USP22, suggesting that USP22 deubiquitinates KDM1A directly (XREF_FIG)."

reach
"In addition, deubiquitination of KDM1A by USP22 was attenuated after GSK3beta knockdown (XREF_FIG)."

reach
"USP22 deubiquitinated LSD1 in RB."

reach
"A screen for DUBs that could stabilize KDM1 demonstrates USP15, USP21, USP22 and USP28 as potential hits, among which ectopic expression of USP22 reduced KDM1A ubiquitination levels strikingly."

reach
"However, of those four DUBs, only USP22 substantially decreased KDM1A ubiquitination (XREF_SUPPLEMENTARY)."

reach
"Furthermore, knockdown of USP22 in GSC11 cells increased KDM1A ubiquitination (XREF_FIG)."
USP22 activates KDM1A.
| 4
USP22 activates KDM1A. 4 / 6
| 4

reach
"Our findings demonstrate that nuclear GSK3beta and USP22 mediated KDM1A stabilization is essential for glioblastoma tumorigenesis."

reach
"miR-140 inhibits osteosarcoma progression by impairing USP22 mediated LSD1 stabilization and promoting p21 expression."

reach
"In contrast, USP22 overexpression in 293T cells increased KDM1A stability (XREF_SUPPLEMENTARY)."

reach
"Likewise, knockdown of USP22 inhibited GSC stemness (XREF_FIG and XREF_SUPPLEMENTARY), and exogenous KDM1A rescued the effect of USP22 depletion on GSC stemness (XREF_FIG and XREF_SUPPLEMENTARY)."
USP22 phosphorylates KDM1A.
| 2
USP22 leads to the phosphorylation of KDM1A. 2 / 2
| 2

reach
"Nuclear GSK3beta promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitylation by USP22."

reach
"Nuclear GSK3beta promotes tumorigenesis by phosphorylating KDM1A and inducing its deubiquitination by USP22."
USP22 increases the amount of KDM1A.
| 2
USP22 increases the amount of KDM1A. 2 / 2
| 2

reach
"We therefore screened a panel of DUBs in which 23 DUBs ' cDNA plasmids were transfected into 293T cells, and found that USP15, USP21, USP22, and USP28 upregulated KDM1A levels (XREF_SUPPLEMENTARY)."

reach
"In GSC11 cells, USP22 knockdown decreased KDM1A protein level (XREF_FIG), but not KDM1A mRNA (XREF_SUPPLEMENTARY)."
USP22 decreases the amount of KDM1A.
| 2
USP22 decreases the amount of KDM1A. 2 / 2
| 2

reach
"A screen for DUBs that could stabilize KDM1 demonstrates USP15, USP21, USP22 and USP28 as potential hits, among which ectopic expression of USP22 reduced KDM1A ubiquitination levels strikingly."

reach
"In GSCs, Knockdown of USP22 causes a decrease in KDM1A protein without affecting KDM1A mRNA expression."
USP22 affects CD274
2 1 | 14 12
USP22 binds CD274.
2 | 2 11
2 | 2 11

sparser
"Now that USP22 could regulate PD-L1 protein level, we asked whether USP22 interacted with PD-L1."

reach
"XREF_BIBR, XREF_BIBR While USP22 interacts with PD-L1 and inhibits PD-L1 ubiquitination, this DUB binds and stabilizes CSN5, suggesting that its PD-L1-regulatory function may involve coordination with CSN5."

sparser
"Thus, we validated the interaction between USP22 and PD-L1."

sparser
"Furthermore, we confirmed the interaction between USP22 and PD-L1 both in HEK293FT and NSCLC cells."

reach
"Our data showed that USP22 interacted with PD-L1 and promoted its stability."

sparser
"In addition, USP22 could facilitated the interaction between CSN5 and PD-L1, and CSN5 promoted the interaction between USP22 and PD-L1."

sparser
"Our results showed that CSN5 enhanced the interaction between USP22 and PD-L1 (Fig.  xref a)."

sparser
"Our data showed that USP22 interacted with PD-L1 and promoted its stability."

sparser
"USP22 physically interacted with PD-L1."

No evidence text available
USP22 deubiquitinates CD274.
1 | 5
USP22 deubiquitinates CD274. 6 / 6
1 | 5

reach
"In addition, USP22 could inhibit the ubiquitination of PD-L1 protein."

reach
"USP22 deubiquitinated PD-L1 and inhibited its proteasome degradation."

reach
"USP22 deubiquitinates CD274 to suppress anti-cancer immunity."

reach
"However, our previous study demonstrated that USP22 induces the deubiquitination of PD-L1 and prevents PD-L1 degradation."

reach
"USP22 can deubiquitinate PD-L1 itself or CSN5 for their stabilization [233] (Figure 3)."
| PMC

"Here, we identified ubiquitin-specific protease 22 (USP22) as a novel deubiquitinase of CD274."
USP22 ubiquitinates CD274.
| 4 1
USP22 ubiquitinates CD274. 5 / 5
| 4 1

reach
"Among them, the tumor-promoting effect of lncRNA KCNQ1OT1 is through the autocrine effect of tumor cell-derived exosomes, which mediates the miR-30a-5p/USP22 pathway to regulate the ubiquitination of PD-L1 and inhibits CD8+ T-cell response, thereby promoting CRC development (Figure 10)."

sparser
"Conclusion Exosomal miR-335-5p promotes ubiquitination of PD-L1 by USP22 through down-regulating USP22, and inhibits TNBC immune escape mediated by PD-L1."

reach
"The tumor-promoting effect of lncRNA KCNQ1OT1 was through the autocrine effect of tumor cell-derived exosomes, which mediates the miR-30a-5p/USP22 pathway to regulate the ubiquitination of PD-L1 and inhibits CD8+ T-cell response, thereby promoting colorectal cancer development.Conclusion: Tumor cell-derived exosomes' KCNQ1OT1 could regulate PD-L1 ubiquitination through miR-30a-5p/USP22 to promote colorectal cancer immune escape."

reach
"Although PD-L1 has been reported to be ubiquitinated or deubiquitinated by CSN5, USP22, OTUB1, FBXO38, STUB1, SPOP or HRD1 [28], only OTUB1 silencing blocked the regulatory effect of PKP3 on PD-L1 expression (Fig. S6D-I, Fig. 6F-G)."

reach
"Conclusion Exosomal miR-335-5p promotes ubiquitination of PD-L1 by USP22 through down-regulating USP22, and inhibits TNBC immune escape mediated by PD-L1."
USP22 activates CD274.
| 3
USP22 activates CD274. 3 / 3
| 3

reach
"Additionally, ubiquitin-specific peptidase 22 (USP22) in HCC [141], ubiquitin-specific peptidase 9, X-linked (USP9X) in OSCC [142], and ubiquitin C-terminal hydrolase L1 (UCHL1) in NSCLC [143] deubiquitinate and upregulate the PD-L1 expression.As a ubiquitously expressed protein, CMTM6 binds PD-L1 either at the plasma membrane or in recycling endosomes, repressing lysosome-mediated degradation of PD-L1 and upregulating protein half-time of PD-L1 without affecting the transcription level of PD-L1 [144, 145]."

reach
"On the one hand, USP22 could directly regulate PD-L1 stability through deubiquitination."

reach
"Our hypothesis is that the poor clinical efficacy of the treatments targeting PD-L1 may be due to the stabilization of PD-L1 mediated by USP22, abolishing the effect of anti-PD-L1 drugs."
ATXN7L3 affects USP22
6 | 6 17
ATXN7L3 binds USP22.
6 | 5 17
6 | 5 4

reach
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

reach
"Further, Pfam analysis of protein domain structures confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar to that found in USP22, which is critical for USP22 interaction with ATXN7L3 and ENY2 and deubiquitination activity (XREF_FIG and XREF_SUPPLEMENTARY)."

No evidence text available

No evidence text available

reach
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) (Lan et al., 2015; Zhang et al., 2008b; Zhao et[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Further, Pfam analysis of protein domain structures (Finn et al., 2014) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As shown in Figure 4 F, we found that association of USP22 and ATXN7L3 was greatly impaired upon addition of increasing amounts of USP27X (compare lane 7 to 8, 9, and 10)."

No evidence text available

sparser
"Immunoblot analysis of purified complexes revealed an interaction between ATXN7L3 and USP22 ( Figure 2 A, lane 1) and between ATXN7L3 and ENY2 ( Figure 2 A, lanes 3 and 7), but not between ENY2 and US[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 10

sparser
"Cotransfection and coimmunoprecipitation experiments revealed that the ATXN7L3 ZnF-Sgf11 domain alone is able to interact with both ENY2 and USP22 as efficiently as the full-length ATXN7L3 (see Figur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Similarly, USP22, the human homolog of Ubp8, is bound to the STAGA complex through interactions with ATXN7L3 and ENY2, which are homologs of Sgf11 and Sus1, respectively ( xref )."

sparser
"The SAGA DUB module is highly conserved both in subunit composition and structural organization ( xref ; xref ; xref ; xref ; xref ; xref ), The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adapter proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( xref ; xref ; xref ), and a fourth protein, ATXN7 (Sgf73), anchors the DUB module to the larger SAGA complex."

sparser
"It has been reported that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex to regulate global levels of H2B monoubiquitination, thereby promoting antibody class switch recombination by facilitating nonhomologous end joining ( xref ; xref ; xref )."

sparser
"Further, Pfam analysis of protein domain structures ( xref ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar to that found in USP22, which is critical for USP22 interaction with ATXN7L3 and ENY2 and deubiquitination activity ( xref and xref ) ( xref )."

sparser
"These results together suggest that ATXN7L3, USP22, and ENY2 form a stable subcomplex and that USP22 and ENY2 are recruited into TFTC/STAGA by ATXN7L3 ( Figure 2 D)."

sparser
"Further, Pfam analysis of protein domain structures ( Finn et al., 2014 ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( Lan et al., 2015; Zhang et al., 2008b; Zhao e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Previous study has shown that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator SAGA complex to regulate global levels of H2B monoubiquitination ( xref )."

sparser
"We show that the ubiquitin protease USP22 forms a subcomplex with ATXN7L3 (ySgf11 homolog) and ENY2 (ySus1 homolog)."
USP22 binds ATXN7L3 and AR. 2 / 2
| 2

sparser
"To further investigate this hypothesis, we analyzed putative interactions of USP22 or ATXN7L3 with AR in mammalian cells."

sparser
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR-dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 1

sparser
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC/STAGA ( Figure 1 D, lane 4)."
ATXN7L3 activates USP22.
| 1
ATXN7L3 activates USP22. 1 / 1
| 1

reach
"Together with SAGA subunit ENY2, ATXN7L3 functions to activate the SAGA deubiquitinase USP22 XREF_BIBR."
USP22 affects cell growth
| 1 21 1
USP22 activates cell growth.
| 1 17
| 1 17

reach
"Second, USP22 significantly increased cell growth in the presence of androgen (XREF_FIG, right)."

reach
"Finally, we discover that USP22 knockdown leads to slower cell growth and reduced tumor size."

reach
"USP22 Promotes Ligand dependent and Castrate resistant PCa Cell Growth."

reach
"Taken together, our results suggest that USP22 promotes NSCLC cell growth in vitro and NSCLC tumorigenesis in vivo, and these effects are through MDMX up-regulation and subsequent p53 inhibition."

eidos
"Our group first demonstrated that knockdown of USP22 induces cell cycle arrest and inhibits cell growth in the HCC cell line HepG2 [ 8] ."

reach
"Third, and most critically, USP22 robustly promoted cell growth and proliferation in the absence of androgen."

reach
"Gain- and loss-of-function assays showed that USP22 promoted gastric cancer cell growth and cell cycle transition while suppressing apoptosis in vitro."

reach
"Our group first ensured that knockdown of USP22 can induce cell cycle arrest and inhibit cell growth in the HCC cell line HepG2 (Ling etal., 2012a)."

reach
"In addition, we present evidence that USP22 promotes Bel/Fu cell growth, migration, invasion, EMT and chemoresistance."

reach
"Our results demonstrated that USP22 silencing suppressed cell growth and induced cell apoptosis."
USP22 inhibits cell growth.
| 4 1
| 4 1

sparser
"These observations indicate that USP22 gene silencing by RNA interference inhibits HCC cell growth (Fig. xref )."

reach
"Hence, we determined whether downregulation of USP22 suppresses colon cancer cell growth and cancer progression."

reach
"USP22 siRNA suppressed cell growth."

reach
"Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora-B, Survivin and Cyclin B, together with the upregulation of cyclin dependent kinase inhibitor 1A (p21)."

reach
"These results suggested that USP22 siRNA effectively inhibited OSCC cell growth in vitro."
USP22 affects FASN
1 | 13 14
USP22 binds FASN.
1 | 14
1 | 14

sparser
"Our study demonstrates that overproduced ROS in colorectal cancer controls lipid synthesis by critically regulating the USP22-FASN axis through a p53-dependent manner."

sparser
"To determine the potential clinical relevance of the USP22-FASN axis, we next assessed the expression of USP22 and FASN proteins in serial sections of 108 human CRC specimens, and found that FASN expression levels were significantly correlated with USP22 levels (Fig. xref , r  = 0.6626, P  < 0.0001)."

sparser
"Thus, the USP22-FASN axis revealed in this study may be a critical mechanism for the maintenance of CSC properties and therapy resistance of human cancer, which deserves further investigation."

sparser
"Because p53 mutation usually loss the transcriptional activity and responses to upstream signals differently [ xref , xref ], p53-mediated repression of the USP22-FASN axis will be abolished in p53-mutated cancers, resulting in FASN stabilization, lipid accumulation, and tumor growth."

No evidence text available

sparser
"Reciprocal immunoprecipitation (IP) assays demonstrated that USP22 and FASN interact with each other in both RKO E6 and HT29 cells (Fig. xref ), which was further confirmed in 293T cells by co-transfection of HA-USP22 and Flag-FASN plasmids (Fig. S xref C)."

sparser
"Our study demonstrates that ROS critically regulates lipid synthesis and tumorigenesis through the USP22-FASN axis in a p53-dependent manner, and targeting the USP22-FASN axis may represent a potential strategy for the treatment of colorectal cancer."

sparser
"These results suggest that H 2 O 2 induces cells apoptosis by repressing the USP22-FASN axis in p53 +/+ colorectal cancer cells."

sparser
"Due to a high-frequency of p53 mutation and dysfunction in human cancer, activation of the USP22-FASN axis may represent a prevailing mechanism that drives tumorigenesis, indicating a promising strategy for the treatment of colorectal cancer."

sparser
"USP22 interacts with FASN and inhibits FASN ubiqutination."
USP22 deubiquitinates FASN.
| 5
USP22 deubiquitinates FASN. 5 / 5
| 5

reach
"Together, these results support that USP22 interacts with FASN and inhibits FASN ubiquitination in CRC cells."

reach
"In p53 wild-type colorectal cancer (CRC) cells, hydrogen peroxide (H 2 O 2 )-induced p53 expression represses the transcription of deubiquitinase USP22, which otherwise deubiquitinates and stabilizes Fatty Acid Synthase (FASN), and thus inhibits fatty acid synthesis."

reach
"Whereas, depletion of USP22 in RKO E6 cells promoted FASN ubiquitination (Fig. 2E)."

reach
"We have found H O -induced p53 expression inhibits the transcription of USP22, which otherwise deubiquitinates and stabilizes FASN."

reach
"Overexpression of USP22 decreased FASN ubiquitination in the presence of MG132 (Fig. 2D and Fig. S2D)."
USP22 increases the amount of FASN.
| 3
USP22 increases the amount of FASN. 3 / 3
| 3

reach
"We, therefore, screened a panel of DUBs by transfecting the cDNA plasmids of 36 DUBs into 293T cells, and found USP2, USP14, USP22, and USP30 upregulated FASN levels (Fig. S2A)."

reach
"As we expected, depletion of USP22 decreased the levels of FASN in CRC cells (Fig. 3A)."

reach
"Moreover, the depletion of USP22 decreased the levels of FASN and Ki-67 in mouse xenograft tumors, and exogenous FASN rescued those effects (Fig. 6H)."
USP22 activates FASN.
| 3
USP22 activates FASN. 3 / 3
| 3

reach
"Together, these results support that USP22 promotes CRC cell proliferation and tumorigenesis by stabilizing FASN."

reach
"While overexpression of USP22 stabilized FASN in 293T cells (Fig. 3B), USP22 depletion promoted FASN degradation in CRC cells under CHX treatment (Fig. 3C)."

reach
"We next investigated the role of USP22-mediated stabilization of FASN in CRC cell proliferation and tumor growth."
USP22 inhibits FASN.
| 2
USP22 inhibits FASN. 2 / 2
| 2

reach
"USP22 interacts with FASN and inhibits FASN ubiqutination."

reach
"While overexpression of USP22 stabilized FASN in 293T cells (Fig. 3B), USP22 depletion promoted FASN degradation in CRC cells under CHX treatment (Fig. 3C)."
USP22 affects ATXN7L3
6 | 5 17
6 | 5 4

reach
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

reach
"Further, Pfam analysis of protein domain structures confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar to that found in USP22, which is critical for USP22 interaction with ATXN7L3 and ENY2 and deubiquitination activity (XREF_FIG and XREF_SUPPLEMENTARY)."

No evidence text available

No evidence text available

reach
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) (Lan et al., 2015; Zhang et al., 2008b; Zhao et[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Further, Pfam analysis of protein domain structures (Finn et al., 2014) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As shown in Figure 4 F, we found that association of USP22 and ATXN7L3 was greatly impaired upon addition of increasing amounts of USP27X (compare lane 7 to 8, 9, and 10)."

No evidence text available

sparser
"Immunoblot analysis of purified complexes revealed an interaction between ATXN7L3 and USP22 ( Figure 2 A, lane 1) and between ATXN7L3 and ENY2 ( Figure 2 A, lanes 3 and 7), but not between ENY2 and US[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 10

sparser
"Cotransfection and coimmunoprecipitation experiments revealed that the ATXN7L3 ZnF-Sgf11 domain alone is able to interact with both ENY2 and USP22 as efficiently as the full-length ATXN7L3 (see Figur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Similarly, USP22, the human homolog of Ubp8, is bound to the STAGA complex through interactions with ATXN7L3 and ENY2, which are homologs of Sgf11 and Sus1, respectively ( xref )."

sparser
"The SAGA DUB module is highly conserved both in subunit composition and structural organization ( xref ; xref ; xref ; xref ; xref ; xref ), The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adapter proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( xref ; xref ; xref ), and a fourth protein, ATXN7 (Sgf73), anchors the DUB module to the larger SAGA complex."

sparser
"It has been reported that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex to regulate global levels of H2B monoubiquitination, thereby promoting antibody class switch recombination by facilitating nonhomologous end joining ( xref ; xref ; xref )."

sparser
"Further, Pfam analysis of protein domain structures ( xref ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar to that found in USP22, which is critical for USP22 interaction with ATXN7L3 and ENY2 and deubiquitination activity ( xref and xref ) ( xref )."

sparser
"These results together suggest that ATXN7L3, USP22, and ENY2 form a stable subcomplex and that USP22 and ENY2 are recruited into TFTC/STAGA by ATXN7L3 ( Figure 2 D)."

sparser
"Further, Pfam analysis of protein domain structures ( Finn et al., 2014 ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( Lan et al., 2015; Zhang et al., 2008b; Zhao e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Previous study has shown that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator SAGA complex to regulate global levels of H2B monoubiquitination ( xref )."

sparser
"We show that the ubiquitin protease USP22 forms a subcomplex with ATXN7L3 (ySgf11 homolog) and ENY2 (ySus1 homolog)."
USP22 binds ATXN7L3 and AR. 2 / 2
| 2

sparser
"To further investigate this hypothesis, we analyzed putative interactions of USP22 or ATXN7L3 with AR in mammalian cells."

sparser
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR-dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 1

sparser
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC/STAGA ( Figure 1 D, lane 4)."
KAT2A affects USP22
9 | 6 8
KAT2A binds USP22.
9 | 3 8
9 | 3 8

sparser
"MACS analysis indicated that there were many genes potentially bound by USP22 or GCN5."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"We found either USP22 antibody or GCN5 antibody precipitated a large number of DNA fragments, indicating that either USP22 or GCN5 widely interacted with different genes in the genome of HeLa cells."

reach
"The polypeptide composition of these purified complexes was assessed by silver staining, which revealed a pattern of 10-12 comigrating proteins shared by the USP22 and hGCN5 complexes."

reach
"This raises the hypothesis that once USP22 associates with SAGA and GCN5, it may oppose telomere recombination in APBs by promoting the binding of POT1 to telomeres via TRF1, thereby inhibiting ATR activation."

reach
"In addition to these motifs, there was no similar motif between USP22 and GCN5 binding sites.The USP22 and GCN5 binding sites had similar distributions across the whole genome."

No evidence text available
KAT2A inhibits USP22.
| 1
KAT2A inhibits USP22. 1 / 2
| 1

reach
"Loss of Gcn5 leads to depletion of Usp22 and the DUB module from SAGA, compromising Usp22 activity, leading to telomere fusions [XREF_BIBR]."
KAT2A activates USP22.
| 2
KAT2A activates USP22. 2 / 2
| 2

reach
"GCN5 has been shown to support the association of USP22 with the SAGA complex."

reach
"Loss of Gcn5 impairs the deubiquitinating activity of Usp22 [XREF_BIBR], which partners with Atxn7 in the DUB module."
| 1 21
| 1 18

reach
"These data suggest that USP22 promotes GC progression by modulating c-Myc/NAMPT/ SIRT1-dependent FOXO1 and YAP signaling."

reach
"USP22 knockdown significantly decreased in vitro survival, proliferation, migration, and invasiveness of GC cells compared with the controls."

reach
"USP22 promotes in vitro GC progression by modulating c-Myc/NAMPT/SIRT1- dependent FOXO1 and YAP signaling pathways."

reach
"In this study, we demonstrated that USP22 mediated protein stabilization of BMI1 promotes gastric CSC stemness maintenance and GC progression, thereby providing a rationale for USP22 targeting as a potential therapeutic approach against GC."

reach
"The mechanistic details regarding how USP22 promotes proliferation and survival in GC cells requires further in depth study."

reach
"In this study, we show that USP22 knockdown significantly decreases migration and invasiveness of GC cells."

reach
"Overall, these results indicate that USP22 promotes GC progression via c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling.Our study has several limitations."

reach
"USP22 silencing inhibits GC cells proliferation."

reach
"USP22 knockdown decreases in vitro proliferation, migration and invasiveness of GC cells."

reach
"Liu et al. reported that USP22 promoted GC progression through the activation of c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways [32]."
| 3

reach
"Knockdown of USP22 suppresses GC xenografts growth."

reach
"Moreover, USP22 knockdown induces apoptosis in GC cells."

reach
"USP22 depletion promotes in vitro GC cell apoptosis."
USP22 affects PALB2
| 13 9
USP22 binds PALB2.
| 8 9
| 8 9

reach
"Upon addition of MBP-PALB2 , USP22 enzymatic activity was robustly activated (Figure 4e) showing that PALB2 directly binds USP22 and stimulates its catalytic activity."

reach
"PALB2 WD40 Domain Directly Binds USP22 and stimulates its Catalytic Activity."

sparser
"To elucidate if USP22 was directly binding PALB2 WD40 we performed in-vitro pulldown experiments using MBP-PALB2 WD40 as the bait along with His-USP22 ( xref )."

sparser
"Furthermore, the lysine residues on PALB2 that USP22 could be potentially deubiquitinating have not been mapped by this study or others and is an excellent future direction for further study on the USP22-PALB2 interaction."

sparser
"Our in-silico analysis showed an interaction between the C-terminal DUB domain of USP22 and the C-terminal WD40 domain of PALB2 that has been previously crystallized ( xref , PDB: 2W18) xref ."

sparser
"Understanding the interaction of USP22-PALB2 and indeed the interaction of other DUBs with WD40 domain containing proteins could present a new way to target DUBs for cancer therapies."

sparser
"We identified a direct interaction between the C-terminal WD40 domain of PALB2 and the DUB domain of USP22 and that this interaction was necessary and sufficient to activate USP22 catalytic DUB activity in-vitro ."

reach
"USP22 interacts with PALB2 and promotes chemotherapy resistance via homologous recombination of DNA double strand breaks."

sparser
"PALB2 WD40 Domain Directly Binds USP22 and stimulates its Catalytic Activity."

reach
"To elucidate if USP22 was directly binding PALB2 we performed in-vitro pulldown experiments using MBP-PALB2 as the bait along with His-USP22 (Figure 4d)."
USP22 increases the amount of PALB2.
| 5
USP22 increases the amount of PALB2. 5 / 5
| 5

reach
"To further validate USP22 was modulating and stabilizing BRCA2 and PALB2 levels at the translational level, cells were depleted of USP22 again with and without treatment of the proteasome inhibitor MG132 to see if this could rescue PALB2 and BRCA2 levels in a USP22 knockdown background (Figure S1c)."

reach
"To determine whether USP22 is modulating PALB2 and BRCA2 protein levels at the transcriptional level we performed qPCR of BRCA2 and PALB2 with and without USP22 knockdown after 48 hours (Figure S1b)."

reach
"USP22 modulates PALB2 and BRCA2 levels to promote chemoresistance in lung adenocarcinoma."

reach
"Lastly, we show USP22 positively regulates BRCA2 and PALB2 levels at the protein level."

reach
"Our study reveals USP22 positively regulates PALB2 and BRCA2 levels at the translational level."
USP22 affects KAT2A
9 | 3 8
9 | 3 8

sparser
"MACS analysis indicated that there were many genes potentially bound by USP22 or GCN5."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"We found either USP22 antibody or GCN5 antibody precipitated a large number of DNA fragments, indicating that either USP22 or GCN5 widely interacted with different genes in the genome of HeLa cells."

reach
"The polypeptide composition of these purified complexes was assessed by silver staining, which revealed a pattern of 10-12 comigrating proteins shared by the USP22 and hGCN5 complexes."

reach
"This raises the hypothesis that once USP22 associates with SAGA and GCN5, it may oppose telomere recombination in APBs by promoting the binding of POT1 to telomeres via TRF1, thereby inhibiting ATR activation."

reach
"In addition to these motifs, there was no similar motif between USP22 and GCN5 binding sites.The USP22 and GCN5 binding sites had similar distributions across the whole genome."

No evidence text available
USP22 affects Histone_H2B
| 19 1
USP22 deubiquitinates Histone_H2B.
| 17
USP22 deubiquitinates Histone_H2B. 10 / 16
| 16

reach
"As we discussed previously, USP22 is a component of a transcriptional activator complex SAGA and can deubiquitinate histones H2A and H2B, as well as several other substrates (Zhang et al., 2008a, b)."

reach
"USP22 is a component of the SAGA transcriptional coactivator complex and can deubiquitinate H2A and H2B [XREF_BIBR - XREF_BIBR]."

reach
"USP22 deubiquitylates both, H2A and H2B."

reach
"Remarkably, USP22, the human ortholog of Ubp8, forms a similar SAGA DUB module and deubiquitinates both H2A and H2B."

reach
"However, de-ubiquitylation of H2B by Usp22, the human homolog of yeast Ubp8, inhibits heterochromatic silencing and promotes gene activation [XREF_BIBR, XREF_BIBR]."

reach
"USP22 was initially reported to promote deubiquitylation of histones H2A and H2B, leading to transcription activation."

reach
"As a subunit of hSAGA, USP22 participates in the deubiquitination of histones H2A and H2B and the acetylation of histone H4 to regulate gene transcription and expression."

reach
"USP22 might de-ubiquitinate H2A and H2B, subunits of the human SAGA complex that are intimately linked to the transcriptional activation of the MYC gene and increased cell proliferation in HCC [XREF_BIBR]."

reach
"The requirement of ATXN7L3 for H2B deubiquitination by USP22, USP27x, and USP51 suggests that the ATXN7L3 zinc finger plays a role analogous to that of the Sgf11 zinc finger in docking human SAGA DUB [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"USP22 may deubiquitinate H2A and H2B, subunits of the hSAGA complex that activate transcription factors and promote carcinogenesis [XREF_BIBR]."
USP22 deubiquitinates Histone_H2B on S2. 1 / 1
| 1

reach
"Deubiquitination of H2B by Ubp8 and USP22 results in the recruitment of Ctk1 leading to Ser2 phosphorylation, a modification associated with elongation."
USP22 ubiquitinates Histone_H2B.
| 2 1
USP22 ubiquitinates Histone_H2B. 3 / 3
| 2 1

reach
"Reduced USP22 Expression Impairs Mitotic Removal of H2B Monoubiquitination, Alters Chromatin Compaction and Induces Chromosome Instability That May Promote Oncogenesis."

sparser
"The modulation of histone H2B ubiquitination by USP22 was shown to underlie the processing of JAK-STAT-inducible genes, suggesting a potential mechanism of USP22 in cancer ."

reach
"The modulation of histone H2B ubiquitination by USP22 was shown to underlie the processing of JAK-STAT-inducible genes, suggesting a potential mechanism of USP22 in cancer [28]."
MYC affects USP22
4 | 1 9 5
MYC binds USP22.
4 | 1 5
4 | 1 5

sparser
"It has been reported that SIRT1 protein level is increased in LSCs in both chronic myeloid leukemia (CML) and acute myeloid leukemia (AML), by either transcriptional induction in CML or by c-Myc-USP22 mediated stabilization of SIRT1 protein in AML [ xref ]."

sparser
"In addition, it has been shown that USP22 interacts with the c-Myc transcription factor in cancer cells ( xref ), and genetic c-Myc suppression impairs iNKT development but with increased PLZF expression ( xref ; xref ), raising the possibility that USP22 represses PLZF expression through its interaction with c-Myc."

No evidence text available

reach
"The data presented here suggest that the recruitment of USP22 to Myc targets as part of the hSAGA complex may provide this critical function.An outstanding question raised by these studies is the iden[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available

No evidence text available

sparser
"However, ChIP analysis failed detect USP22 binding to PLZF promoter DNA, together with the fact that USP22 interaction with c-Myc enhances but not suppresses c-Myc transcriptional activity ( xref ), largely excluding the possibility that USP22 inhibits PLZF transcription through c-Myc."

No evidence text available

sparser
"These results support a role for USP22 in MYC-mediated increase in SIRT1 protein stabilization, and indicate that FLT3-ITD, c-MYC and USP22 form an oncogenic network that enhances SIRT1 expression and activity in leukemic cells."

sparser
"Mechanically, USP22 interacted with c-Myc to promote its stabilization by deubiquitination in TNBC cells."
MYC activates USP22.
| 4
MYC activates USP22. 4 / 5
| 4

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"At the posttranscriptional level, c-MYC has been shown to increase USP22 protein but not mRNA levels."

reach
"Furthermore, USP22 acts as an enzymatic component of the SAGA transcriptional cofactor complex and is activated by Myc as an oncogene [38]."
| PMC

reach
"For example, as part of the SAGA complex USP22 promotes transcriptional activation by the Myc oncogene (Zhang et al., 2008b)."

reach
"This SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability."
MYC increases the amount of USP22.
| 3
MYC increases the amount of USP22. 3 / 3
| 3

reach
"This is significant, as AR upregulation drives the CRPC phenotype, MYC is a known PCa oncogene, and USP22 regulates MYC transcription."

reach
"Importantly, c-MYC has been reported to induce the expression of the deubiquitinase USP22, which in turn reduced ubiquitination and enhanced the stability of SIRT1 in CD34 + Flt3-ITD cells."

reach
"These results suggest that USP22 positively regulates MYC dependent transcription, which may at least partially explain its oncogenic properties."
MYC inhibits USP22.
| 1 1
MYC inhibits USP22. 2 / 2
| 1 1

reach
"The results showed also that USP22 is a positive regulator of c-Myc-dependent transcription and induction of c-Myc targeted genes is impaired in USP22 depleted cells."

eidos
"In summary , our results demonstrate that USP22 expression is promoted by AP2 and c-Myc and is suppressed by SP1 and ATF3 at the transcriptional level ."
USP22 affects PTGS2
4 | 10 3
USP22 binds PTGS2.
4 | 2 3
4 | 2 3

No evidence text available

No evidence text available

reach
"As shown in Fig. 2 C, USP22 was pulled down together with COX-2 but not with COX-1, confirming the specificity of the interaction between USP22 and COX-2."

reach
"To verify the direct interaction between USP22 and COX-2, recombinant USP22 was incubated with His tagged COX-2 or COX-1 and proteins were isolated by affinity chromatography."

sparser
"To verify the direct interaction between USP22 and COX-2, recombinant USP22 was incubated with His-tagged COX-2 or COX-1 and proteins were isolated by affinity chromatography."

sparser
"To examine the potential interaction between USP22 and COX-2, A549 cells were transfected with vectors expressing USP22 and Myc-tagged COX-2 and cell lysates were immunoprecipitated against anti-Myc [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As shown in C, USP22 was pulled down together with COX-2 but not with COX-1, confirming the specificity of the interaction between USP22 and COX-2."

No evidence text available

No evidence text available
USP22 activates PTGS2.
| 3
USP22 activates PTGS2. 3 / 4
| 3

reach
"Our results showed that USP22 silencing downregulated COX-2 and FBP1 in A549 and NCI-H460 cells compared to control siRNA."

reach
"Here, we identified COX-2 as a substrate of USP22 and investigated the role of USP22 in tumorigenesis via the modulation of COX-2 stability and activity.In the present study, we showed that silencing [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Silencing of USP22 downregulated COX-2, decreased its half-life, and inhibited lung carcinoma cell proliferation by directly interacting with and modulating the stability and activity of COX-2 through the regulation of its ubiquitination status."
USP22 increases the amount of PTGS2.
| 3
USP22 increases the amount of PTGS2. 2 / 2
| 2

reach
"The modulation of COX-2 levels by ubiquitination and the importance of COX-2 and PGE2 signaling in lung cancer have been demonstrated; therefore, our findings indicating the modulation of COX-2 levels[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The present findings showing the modulation of COX-2 and PGE2 expression by USP22 mediated deubiquitination of COX-2 and its effect on cell viability in lung carcinoma cells suggests a potential mecha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Modified USP22 increases the amount of PTGS2. 1 / 1
| 1

reach
"Ectopic expression of USP22 upregulated the levels of COX-2, whereas expression of the catalytically inactive C185A USP22 mutant had no effect, confirming that USP22 regulates the stability of COX-2 i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 decreases the amount of PTGS2.
| 2
USP22 decreases the amount of PTGS2. 2 / 3
| 2

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"Silencing of USP22 or COX-2 significantly decreased the production of PGE2, whereas overexpression of COX-2 restored PGE2 levels downregulated by USP22, confirming that USP22 modulates COX-2 expressio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The results of western blot analysis showed that USP22R restored the levels of USP22 and COX-2 downregulated by USP22 siRNA."
USP22 affects Neoplasms
| 7 10
USP22 activates Neoplasms.
| 6 9
| 6 9

reach
"USP22 has been reported to promote tumor progression by participating in the mediation of DNA repair processes [38]."

reach
"Consistent with these findings, our data demonstrate that USP22 promotes gastric cancer cell proliferation, migration, and invasion in vitro and enhances tumor growth in vivo."

reach
"We performed rescue experiments to test whether ALKBH5’s tumor-promoting function may be mediated by USP22 and RNF40."

reach
"In vivo experiments reveal that USP22 knockdown in GC cells significantly reduces xenograft tumor growth and lung metastasis in SCID mice."

eidos
"Despite these advances , the overall mechanisms by which USP22 contributes to cancer progression remain incompletely defined ."

reach
"Our study also shows that USP22 silencing in GC cells decreases cell proliferation and induces cell cycle arrest and apoptosis in vitro, and suppresses tumor growth and metastasis in vivo."

eidos
"To date , no small molecule inhibitors of USP22 have been reported , but given mounting evidence in multiple contexts that USP22 promotes tumor progression , the development of such inhibitors would be desirable ."

reach
"USP22 and RNF40 mediate tumor-promoting function of ALKBH5."

eidos
"In sum , these studies identify USP22 as a regulator of the response to DNA damage , and ultimately define a major node by which USP22 promotes cancer phenotypes ."

eidos
"A more recently published report indicates that USP22 may promote tumor progression and induce EMT in colorectal carcinoma patients [ 13 ] ."
USP22 inhibits Neoplasms.
| 1 1
| 1 1

reach
"Interestingly, it was demonstrated that silencing USP22 inhibited proliferation in bladder cancer cells (Lv et al., 2011) leading to cell cycle arrest, inhibition of autophagy and decreased tumor progression representing a potential target for cancer therapy."

eidos
"Apart from activating oncogenes such as BMI-1 and c-MYC , USP22 can inhibit the expression of tumor suppressors such as TP53 through ubiquitination , thus promoting proliferation of tumors [ 87 ] ."
USP22 affects MDM4
2 | 10 6
USP22 binds MDM4.
2 | 7 6
2 | 7 6

reach
"MDMX Directly Binds to USP22 in NSCLC Cells."

reach
"Furthermore, we confirmed that MDMX directly interacts with endogenous USP22 in NCl-H460 cells, as MDMX was detected in USP22 immunoprecipitates and vice versa (XREF_FIG C, D)."

reach
"To investigate the interaction between MDMX and USP22, co-immunoprecipitation analysis was performed in NSCLC cell lines."

reach
"The interaction between USP22 and MDMX in NSCLC cells was studied using co-immunoprecipitation."

No evidence text available

No evidence text available

sparser
"Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells."

sparser
"MDMX Directly Binds to USP22 in NSCLC Cells."

reach
"Our data suggest that MDMX directly binds to USP22 in NSCLC cells."

sparser
"Furthermore, we confirmed that MDMX directly interacts with endogenous USP22 in NCl-H460 cells, as MDMX was detected in USP22 immunoprecipitates and vice versa ( xref C,D)."
USP22 increases the amount of MDM4.
| 3
USP22 increases the amount of MDM4. 3 / 3
| 3

reach
"Additionally, USP22 silencing downregulates MDMX protein expression and activates the p53 pathway."

reach
"In addition, similar to our in vitro findings, USP22 silencing led to a decreased level of MDMX and increased levels of p53 pathway proteins in xenograft tumor tissues (XREF_FIG C)."

reach
"Interestingly, we found that in A549 and NCI-H460 cells, USP22 silencing, while activating the p53 pathway, decreased MDMX protein expression (XREF_FIG C), which was confirmed with immunofluorescence (IF) analysis (XREF_FIG D)."
MDM4 affects USP22
2 | 10 6
MDM4 binds USP22.
2 | 7 6
2 | 7 6

reach
"MDMX Directly Binds to USP22 in NSCLC Cells."

reach
"Furthermore, we confirmed that MDMX directly interacts with endogenous USP22 in NCl-H460 cells, as MDMX was detected in USP22 immunoprecipitates and vice versa (XREF_FIG C, D)."

reach
"To investigate the interaction between MDMX and USP22, co-immunoprecipitation analysis was performed in NSCLC cell lines."

reach
"The interaction between USP22 and MDMX in NSCLC cells was studied using co-immunoprecipitation."

No evidence text available

No evidence text available

sparser
"Our co-immunoprecipitation analysis shows that USP22 interacts with MDMX in NSCLC cells."

sparser
"MDMX Directly Binds to USP22 in NSCLC Cells."

reach
"Our data suggest that MDMX directly binds to USP22 in NSCLC cells."

sparser
"Furthermore, we confirmed that MDMX directly interacts with endogenous USP22 in NCl-H460 cells, as MDMX was detected in USP22 immunoprecipitates and vice versa ( xref C,D)."
MDM4 activates USP22.
| 3
MDM4 activates USP22. 3 / 3
| 3

reach
"Importantly, overexpression of MDMX reversed USP22 silencing, induced p53 activation, growth inhibition, cell cycle arrest and apoptosis in A549 cells (XREF_FIG B-E)."

reach
"These results demonstrate that MDMX mediates USP22 's regulation effect in the NSCLC cell line."

reach
"MDMX Mediates USP22 's Regulation Effect in NSCLC Cells."
USP22 affects cisplatin
| 17
USP22 activates cisplatin.
| 9
| 9

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"USP22 Induces Cisplatin Resistance in Lung Adenocarcinoma by Regulating gammaH2AX Mediated DNA Damage Repair and Ku70 and Bax Mediated Apoptosis."

reach
"According to that model, USP22 enhances DNA damage repair and cisplatin resistance by deubiquitinating histone H2A, which in turn facilitates the phosphorylation of histone H2AX."

reach
"Combining with our previous results, we concluded that both USP22 and Sirt1 can induce cisplatin resistance, but Sirt1 overexpression ca n't phenocopy USP22 mediated cisplatin resistance."

reach
"The study reveal the dual mechanism of USP22 involvement in cisplatin resistance : (1) USP22 enhances DNA damage repair and induce cisplatin resistance by promoting the phosphorylation of histone H2AX via deubiquitinating histone H2A."

reach
"These results confirm that USP22 is involved in the cisplatin resistance of A549 and CDDP cells and H2AX, gammaH2AX, and Sirt1 may be responsible for USP22 mediated cisplatin resistance."

reach
"To verify whether inhibition of USP22 expression could reverse the cisplatin resistance of A549 and CDDP cells, CCK8 assays showed that, after the inhibition of USP22 expression, the 48h IC50 of A549 and CDDP decreased from 0.925 +/- 0.04 muM to 0.337 +/- 0.03 muM."

reach
"To verify whether inhibition of USP22 expression could reverse the cisplatin resistance of A549 and CDDP cells, CCK8 assays showed that, after the inhibition of USP22 expression, the 48h IC50 of A549 and CDDP decreased from 0.925 +/- 0.04 muM to 0.337 +/- 0.03 muM."

reach
"Moreover, the resistance degree of USP22 mediated cisplatin resistance was higher than Sirt1 mediated cisplatin resistance."

reach
"To further confirm that USP22 induces cisplatin resistance via Sirt1, we added flow cytometric analysis results."
USP22 inhibits cisplatin.
| 8
| 8

reach
"In addition, the cisplatin sensitivity in cisplatin resistant A549 and CDDP cells was restored by USP22 inhibition in vivo and vitro."

reach
"The cisplatin sensitivity in cisplatin resistant A549 and CDDP cells was restored by USP22 inhibition in vivo and vitro."

reach
"The Cisplatin Sensitivity in Cisplatin Resistant A549 and CDDP Cells Was Restored by USP22 Inhibition."

reach
"These results suggest that inhibiting USP22 expression enhanced cisplatin sensitivity in lung adenocarcinoma by downregulation of Sirt1 and gammaH2AX in vivo."

reach
"Furthermore, USP22 knockout significantly impaired non homologous DNA damage repair capacity, enhanced cisplatin and irradiation induced apoptosis in these cells."

reach
"These results indicate that the cisplatin sensitivity in cisplatin resistant A549 and CDDP cells was restored by USP22 inhibition."

reach
"Silencing USP22 can inhibit the Wnt/β-catenin pathway to reduce cell stemness and enhance the sensitivity of PC cells to cisplatin."

reach
"Inhibiting USP22 Expression Enhanced Cisplatin Sensitivity in Cisplatin Resistant A549 and CDDP Cell Nude Mouse Xenografts."
USP22 affects TP53
| 1 13 1
USP22 inhibits TP53.
| 1 10
USP22 inhibits TP53. 10 / 13
| 1 10

reach
"Intriguingly, we found that USP22 silencing activates the p53 pathway in human NSCLC cells and tumor tissues along with downregulation of MDMX protein, a major negative regulator of p53."

reach
"USP22 Silencing Down-Regulates MDMX and Up-Regulates the p53 Pathway in NSCLC Cells."

reach
"It has been reported that USP22 antagonizes p53 in bladder cancer cells through up-regulating MDM2 [XREF_BIBR]."

reach
"Hence USP22 silencing reduces the capacity of FBP1 to repress p21 (independently of TP53 status), which in turn inhibits CDKs to prevent the G1/S transition and resulting in G1 accumulation [XREF_BIBR]."

reach
"As for Myc, USP22 depletion blocked the ability of p53 to activate the transcription of its targets."

reach
"In retinoblastoma, the depletion of USP22 has been shown to induce cancer cell apoptosis by suppressing the TERT/P53 signal pathway ."

reach
"Importantly, overexpression of MDMX reversed USP22 silencing, induced p53 activation, growth inhibition, cell cycle arrest and apoptosis in A549 cells (XREF_FIG B-E)."

reach
"Several studies demonstrated that USP22 silencing could activate p53."

reach
"On the bases of these results, we speculated that USP22 silencing activates the p53 pathway in NSCLC cells by post-transcriptional down-regulation of MDMX."

reach
"USP22 may antagonize p53 through Sirt1 stabilization to suppress cell apoptosis under DNA damage and during embryonic development (Lin etal., 2012)."
USP22 activates TP53.
| 3 1
USP22 activates TP53. 4 / 4
| 3 1

sparser
"Several studies demonstrated that USP22 silencing could activate p53. xref , xref Because USP22, Ube2d4, and Ube3b were important downstream genes of YWHAZ, we infer that YWHAZ downregulates p53 by activating USP22, Ube2d4, and Ube3b, which make P53 ubiquitination and lead to its proteasomal degradation."

reach
"Silencing of USP22 promotes human retinoblastoma cell apoptosis by inhibiting TERT and P53 pathway 36."

reach
"USP22 promotes hypoxia induced HCC stemness by a HIF1alpha and USP22 positive feedback loop on TP53 inactivation."

reach
"USP22 promotes hypoxia induced hepatocellular carcinoma stemness by a HIF1alpha and USP22 positive feedback loop upon TP53 inactivation."
USP22 affects TERF1
1 | 12 3
USP22 deubiquitinates TERF1.
1 | 5
USP22 deubiquitinates TERF1. 6 / 6
1 | 5

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"For example, USP22 promotes TRF1 deubiquitylation to enhance TRF1 protein stability and maintain telomere integrity."

reach
"Additionally, Usp22 directly deubiquitinates TRF1 (TBP (TATA box binding protein)-related factor 1) to regulate the transcription of cell cycle and apoptosis genes [XREF_BIBR] and inhibits the transcriptional activity of p53 by deubiquitinating SIRT1 histone deacetylase [XREF_BIBR] and by regulating MDMX stability [XREF_BIBR]."

reach
"Given the known regulation of TRF1 by ubiquitination, we hypothesized that the SAGA complex might facilitate Usp22 dependent deubiquitination of TRF1 and that loss of Gcn5 might alter this activity by compromising complex integrity."

reach
"GCN5 and USP22 also protect telomeres from DNA damage response through the stabilization of a shelterin component called TRF1, and interestingly, this regulation is not transcriptional but involves USP22 mediated deubiquitination of TRF1 [XREF_BIBR]."

reach
"This dissociation leads to lowered USP22 activity, which in turn leads to increased ubiquitination and turnover of TRF1 (XREF_FIG)."
USP22 binds TERF1.
| 3 3
| 3 3

reach
"USP22 could bind to TRF1 and regulate telomere length (Atanassov etal., 2009)."

sparser
"For example, USP22 binding to TRF1, a protein that regulates telomere length, induces TRF1 protein stability."

sparser
"USP22 could bind to TRF1 and regulate telomere length (Atanassov et al ., xref )."

reach
"USP22 interacts with TRF1 and is required for TRF1 stability."

reach
"For example, USP22 binding to TRF1, a protein that regulates telomere length, induces TRF1 protein stability."

sparser
"USP22 interacts with TRF1 and is required for TRF1 stability."
USP22 increases the amount of TERF1.
| 3
Modified USP22 increases the amount of TERF1. 2 / 2
| 2

reach
"Conversely, overexpression of wild-type (but not catalytically inactive) USP22 leads to increased TRF1 levels."

reach
"Furthermore, expression of wt-USP22, but not the C185S mutant, was able to partially restore TRF1 levels in cells depleted for endogenous USP22 (XREF_FIG, compare panels 4, 5 and 6)."
USP22 increases the amount of TERF1. 1 / 2
| 1

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"Depleting USP22 decreases TRF1 levels and enhances cell death by genotoxic insults ."
USP22 activates TERF1.
| 1
USP22 bound to TERF1 activates TERF1. 1 / 1
| 1

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"For example, USP22 binding to TRF1, a protein that regulates telomere length, induces TRF1 protein stability."
USP22 affects AKT
| 16
USP22 activates AKT.
| 11
USP22 activates AKT. 10 / 11
| 11

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"XREF_FIG A, knockdown of USP22 by shRNA inhibited the AKT and MRP1 pathway compared with control shRNA cells and wild-type cells."

reach
"Previous study also showed that USP22 promotes cell cycle progression by positively regulating the PI3K and Akt pathway [XREF_BIBR]."

reach
"USP22 overexpression in gastric cancer cells induces the upregulation of SOS1 and activation of the RAS/ERK and PI3K/AKT pathways."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS and ERK and PI3K and AKT pathways in SGC7901 cells and xenograft tumor tissues."

reach
"Previous studies have confirmed that USP22 can promote the biological process of NSCLC cells by regulating BMI-1 and AKT signaling pathway [XREF_BIBR]."

reach
"These results suggest that USP22 downregulation inhibits OS cells by suppressing the PI3K and Akt pathway."

reach
"We observed that USP22 could positively regulate the AKT pathway in a SIRT1 dependent manner."

reach
"Similarly, overexpression of USP22 in BEL/7402 cells activated the AKT and MRP1 pathway."

reach
"3.5 USP22 activates the AKT and MRP1 pathway depending on SIRT1 in HCC cells."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues."
USP22 inhibits AKT.
| 3
USP22 inhibits AKT. 3 / 4
| 3

reach
"Furthermore, our results showed that USP22 deletion also caused down-regulation of Akt and GSK3beta activity, which can also contribute to the reduction of cyclin D2."

reach
"Silencing Smad4 blocked USP22 knockdown induced Akt inhibition in Bel/Fu cells."

reach
"Downregulation of USP22 Inhibited the Activation of PI3K and Akt Signaling Pathway."
USP22 increases the amount of AKT.
| 2
USP22 increases the amount of AKT. 2 / 2
| 2

reach
"We have reported that USP22 mediates cell survival and proliferation by promoting the expression of BMI-1 and upregulation of activated AKT pathway in colon cancer cells."

reach
"USP22 knockdown decreased MDR related genes expression through up-regulation of Smad4 and suppression of Akt."
USP22 affects ABCC1
| 6 11
USP22 activates ABCC1.
| 6 5
USP22 activates ABCC1. 10 / 11
| 6 5

reach
"Simply put, USP22 may activate the SIRT1–AKT–MRP1 pathway and consequently promote MDR in human HCC cells (226)."

eidos
"The downregulation of USP22 suppresses multidrug resistance-associated protein 1 ( MRP1 ) to induce intracellular sorafenib accumulation and hampers glycolysis of HCC cells ."

reach
"Similarly, overexpression of USP22 in BEL/7402 cells activated the AKT and MRP1 pathway."

eidos
"iv ) The downregulation of USP22 not only suppresses multidrug resistance-associated protein 1 ( MRP1 ) , enhances the intracellular accumulation of sorafenib , and finally inhibits cell proliferation and cancer angiogenesis , but also inhibits glycolysis in hepatocellular carcinoma ( HCC ) cells , enhancing sorafenib chemosensitivity and impairing cell metabolism ."

reach
"Both of these findings indicated that USP22 upregulated MRP1 depending on the AKT pathway."

reach
"3.5 USP22 activates the AKT and MRP1 pathway depending on SIRT1 in HCC cells."

reach
"XREF_FIG A, knockdown of USP22 by shRNA inhibited the AKT and MRP1 pathway compared with control shRNA cells and wild-type cells."

eidos
"] Our study provided strong evidence that the downregulation of USP22 by Gal-SLPs suppressed the expression of MRP1 and caused high intracellular sorafenib accumulation ."

eidos
"During sorafenib treatment , upregulation of USP22 increases ABCC1 expression and subsequently contributes to sorafenib resistance in HCC cells ."

eidos
"] Downregulation of USP22 could inhibit the AKT / GSK-3beta pathway and further suppress the expression of MRP1 ( Figure 4a [ ."
USP22 increases the amount of ABCC1.
| 4
USP22 increases the amount of ABCC1. 4 / 4
| 4

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"LY294002 (10mum) also suppressed USP22 induced high expression of MRP1 via inhibition of AKT pathway in BEL7402 cells."

reach
"Subsequently, using qPCR array analysis, we found that knockdown of USP22 could drastically inhibit the expression of MRP1, but not P-gp, in BEL/FU cells."

reach
"Collectively, USP22 might deubiquitinate SIRT1 and subsequently activate the AKT pathway, increasing the expression of MRP1 to induce MDR in HCC cells."

reach
"During sorafenib treatment, upregulation of USP22 increases ABCC1 expression and subsequently contributes to sorafenib resistance in HCC cells."
USP22 decreases the amount of ABCC1.
| 2
USP22 decreases the amount of ABCC1. 2 / 2
| 2

reach
"3.4 PCR array results imply that downregulation of USP22 in BEL/FU cells decreases the expression of MRP1, but not P-gp."

reach
"Downregulation of USP22 dramatically inhibited the expression of ABCC1 (encoding MRP1) but weakly influenced ABCB1 (encoding P-glycoprotein)."
PALB2 affects USP22
| 8 9
| 8 9

reach
"Upon addition of MBP-PALB2 , USP22 enzymatic activity was robustly activated (Figure 4e) showing that PALB2 directly binds USP22 and stimulates its catalytic activity."

reach
"PALB2 WD40 Domain Directly Binds USP22 and stimulates its Catalytic Activity."

sparser
"To elucidate if USP22 was directly binding PALB2 WD40 we performed in-vitro pulldown experiments using MBP-PALB2 WD40 as the bait along with His-USP22 ( xref )."

sparser
"Furthermore, the lysine residues on PALB2 that USP22 could be potentially deubiquitinating have not been mapped by this study or others and is an excellent future direction for further study on the USP22-PALB2 interaction."

sparser
"Our in-silico analysis showed an interaction between the C-terminal DUB domain of USP22 and the C-terminal WD40 domain of PALB2 that has been previously crystallized ( xref , PDB: 2W18) xref ."

sparser
"Understanding the interaction of USP22-PALB2 and indeed the interaction of other DUBs with WD40 domain containing proteins could present a new way to target DUBs for cancer therapies."

sparser
"We identified a direct interaction between the C-terminal WD40 domain of PALB2 and the DUB domain of USP22 and that this interaction was necessary and sufficient to activate USP22 catalytic DUB activity in-vitro ."

reach
"USP22 interacts with PALB2 and promotes chemotherapy resistance via homologous recombination of DNA double strand breaks."

sparser
"PALB2 WD40 Domain Directly Binds USP22 and stimulates its Catalytic Activity."

reach
"To elucidate if USP22 was directly binding PALB2 we performed in-vitro pulldown experiments using MBP-PALB2 as the bait along with His-USP22 (Figure 4d)."
CCNB1 affects USP22
4 | 5 7
4 | 5 7

reach
"USP22 binding to Cyclin B1, promotes cyclin B1 accumulation in the nucleus and inhibits its degradation [XREF_BIBR]."

sparser
"To further refine our understanding of the molecular interaction between USP22 and CCNB1, we generated truncated USP22 mutants ( xref )."

No evidence text available

sparser
"However, this report clearly demonstrates that USP22 binds and deubiquitinates cyclin B1, leading to its stabilization."

No evidence text available

sparser
"The interaction between endogenous USP22 and CCNB1 in human colon cancer cells was also detected, as anti-CCNB1-specific antibody but not normal mouse immunoglobulin G immunoprecipitated USP22 protein ( xref )."

sparser
"In addition, as S237 is also within the portion of USP22 that interacts with CCNB1, it is possible that CDK1-mediated S237 phosphorylation enhances USP22 interaction with CCNB1."

sparser
"USP22 interacts with CCNB1."

No evidence text available

sparser
"USP22 binding to Cyclin B1, promotes cyclin B1 accumulation in the nucleus and inhibits its degradation [ xref ]."
USP22 affects H2Bub1
| 16
USP22 activates H2Bub1.
| 7
USP22 activates H2Bub1. 7 / 7
| 7

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"To test this possibility, we sought to determine whether reduced USP22 expression impairs H2Bub1 removal specifically within prophase chromosomes."

reach
"Interestingly however, this compensatory mechanism does not function in all cellular processes in which USP22 mediated H2Bub1 regulation is involved, including transcriptional activation and DNA damage repair [XREF_BIBR, XREF_BIBR, XREF_BIBR] (see Section 6 and Section 9)."

reach
"Using complementary genetic and QuantIM approaches, we show that USP22 silencing impairs H2Bub1 removal from chromosomes during prophase and correlates with increases in multiple CIN phenotypes."

reach
"Mechanistically, USP22 depletion in human CRC cells induced a profound upregulation of secreted protein acidic and rich in cysteine (SPARC) by affecting H3K27ac and H2Bub1 occupancy on the SPARC gene."

reach
"Consistent with that finding is another study that implicates the ubiquitin protease, USP22, which targets H2Bub1 for turnover in malignant colon carcinoma."

reach
"Taken together with previous findings by others that USP22 is overexpressed in many cancers and our findings that ATXN7L3 and ENY2 levels are normally limiting in cells, these results suggest that imb[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The deubiquitinating enzyme USP22 catalyzes H2Bub1 removal in interphase and may also be required for H2Bub1 removal in early mitosis to maintain chromosome stability."
USP22 deubiquitinates H2Bub1.
| 4
USP22 deubiquitinates H2Bub1. 4 / 4
| 4

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"Thus, ATXN7L3 is required for the full activity of the three related DUB modules to regulate global H2Bub1 levels, whereas USP22-containing DUB module is less involved in genome-wide deubiquitylation of H2Bub1."

reach
"Unlike the ATXN7L3 DUB complex, a USP22, ATXN7L3B, and ENY2 complex can not deubiquitinate H2Bub1 efficiently in vitro Moreover, ATXN7L3B knockdown inhibits migration of breast cancer cells in vitro and limits expression of ER target genes."

reach
"Along these lines it is interesting to note that neither free USP22 nor a stable recombinant subcomplex, composed of TAF5L, ATXN7L3, ENY2, and USP22, can deubiquitinate H2Aub1 or H2Bub1 in vitro, sugg[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Finally, USP22 and the 2A-DUB (KIAA1915), both target H2Aub1 (although USP22 can also deubiquitylate H2Bub1), and both were described as co-activators of androgen receptor (AR)-mediated transcription."
USP22 inhibits H2Bub1.
| 3
USP22 inhibits H2Bub1. 3 / 3
| 3

reach
"We show that USP22 deficiency impairs H2Bub1 removal and induces chromatin compaction defects."

reach
"Western blot analysis of H2Bub1 abundance within asynchronous USP22 silenced and control cells indicates that USP22 silencing induces a moderate increase (1.1- to 1.5-fold) in the global abundance of H2Bub1."

reach
"In addition, we reveal that USP22 deficiency impairs H2Bub1 removal in early mitosis and induces CIN."
USP22 increases the amount of H2Bub1.
| 2
USP22 increases the amount of H2Bub1. 2 / 2
| 2

reach
"Similarly, Atanassov et al recently reported that depletion of USP22, a major H2B DUB, not only failed to increase H2Bub1 levels but even caused a mild decrease; this was ascribed to the fact that two newly identified H2B DUBs, USP27X and USP51, compete with USP22 for binding to the SAGA complex adaptor proteins ATXN7L3 and ENY2 XREF_BIBR."

reach
"In this study, we demonstrate that siRNA mediated USP22 depletion increases H2Bub1 levels in early mitosis and induces CIN phenotypes associated with mitotic chromatin compaction defects revealed by super-resolution microscopy."
FASN affects USP22
1 | 1 14
FASN binds USP22.
1 | 14
1 | 14

sparser
"Our study demonstrates that overproduced ROS in colorectal cancer controls lipid synthesis by critically regulating the USP22-FASN axis through a p53-dependent manner."

sparser
"To determine the potential clinical relevance of the USP22-FASN axis, we next assessed the expression of USP22 and FASN proteins in serial sections of 108 human CRC specimens, and found that FASN expression levels were significantly correlated with USP22 levels (Fig. xref , r  = 0.6626, P  < 0.0001)."

sparser
"Thus, the USP22-FASN axis revealed in this study may be a critical mechanism for the maintenance of CSC properties and therapy resistance of human cancer, which deserves further investigation."

sparser
"Because p53 mutation usually loss the transcriptional activity and responses to upstream signals differently [ xref , xref ], p53-mediated repression of the USP22-FASN axis will be abolished in p53-mutated cancers, resulting in FASN stabilization, lipid accumulation, and tumor growth."

No evidence text available

sparser
"Reciprocal immunoprecipitation (IP) assays demonstrated that USP22 and FASN interact with each other in both RKO E6 and HT29 cells (Fig. xref ), which was further confirmed in 293T cells by co-transfection of HA-USP22 and Flag-FASN plasmids (Fig. S xref C)."

sparser
"Our study demonstrates that ROS critically regulates lipid synthesis and tumorigenesis through the USP22-FASN axis in a p53-dependent manner, and targeting the USP22-FASN axis may represent a potential strategy for the treatment of colorectal cancer."

sparser
"These results suggest that H 2 O 2 induces cells apoptosis by repressing the USP22-FASN axis in p53 +/+ colorectal cancer cells."

sparser
"Due to a high-frequency of p53 mutation and dysfunction in human cancer, activation of the USP22-FASN axis may represent a prevailing mechanism that drives tumorigenesis, indicating a promising strategy for the treatment of colorectal cancer."

sparser
"USP22 interacts with FASN and inhibits FASN ubiqutination."
FASN activates USP22.
| 1
FASN activates USP22. 1 / 1
| 1

reach
"We found that USP22 depletion in HT29 and RKO E6 cells attenuated tumor formation, and reconstituted expression of FASN rescued the inhibitory effect of USP22 depletion on colorectal tumorigenesis (Fig. 6E–G)."
ATXN7 affects USP22
8 | 5 1
ATXN7 binds USP22.
8 | 1 1
8 | 1

No evidence text available

reach
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC and STAGA."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
| 1

sparser
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC/STAGA ( Figure 1 D, lane 4)."
ATXN7 inhibits USP22.
| 4
ATXN7 inhibits USP22. 3 / 4
| 3

reach
"Recently, Lan et al. reported that poly (Q) Ataxin-7 does not directly decrease USP22 enzymatic activity, but instead, it forms aggregates that impair USP22 binding to its substrates [XREF_BIBR]."

reach
"For example, polyQ ataxin-7 sequesters USP22 into aggregates and inhibits its DUB activity."

reach
"This indicated that poly (Q) Ataxin-7 likely decreased USP22 activity."
Mutated ATXN7 inhibits USP22. 1 / 1
| 1

reach
"As the Ubp8 ortholog USP22 was recently shown to interact with, deubiquitinate, and stabilize the Sir2 ortholog Sirt1, and conversely Sirt1 has been shown to mediate deacetylation of USP22 and the SAGA coactivator complex, the discovery of genetic and functional relationships between Sgf73, Ubp8, and Sir2 in yeast strongly suggests that mutant ataxin-7 protein could be impairing the function of not only Gcn5 in the context of the STAGA complex, but also USP22 in the deubiquitinase module."
USP22 affects ENY2
2 | 2 11
| 10

sparser
"Cotransfection and coimmunoprecipitation experiments revealed that the ATXN7L3 ZnF-Sgf11 domain alone is able to interact with both ENY2 and USP22 as efficiently as the full-length ATXN7L3 (see Figur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Similarly, USP22, the human homolog of Ubp8, is bound to the STAGA complex through interactions with ATXN7L3 and ENY2, which are homologs of Sgf11 and Sus1, respectively ( xref )."

sparser
"The SAGA DUB module is highly conserved both in subunit composition and structural organization ( xref ; xref ; xref ; xref ; xref ; xref ), The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adapter proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( xref ; xref ; xref ), and a fourth protein, ATXN7 (Sgf73), anchors the DUB module to the larger SAGA complex."

sparser
"It has been reported that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex to regulate global levels of H2B monoubiquitination, thereby promoting antibody class switch recombination by facilitating nonhomologous end joining ( xref ; xref ; xref )."

sparser
"Further, Pfam analysis of protein domain structures ( xref ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar to that found in USP22, which is critical for USP22 interaction with ATXN7L3 and ENY2 and deubiquitination activity ( xref and xref ) ( xref )."

sparser
"These results together suggest that ATXN7L3, USP22, and ENY2 form a stable subcomplex and that USP22 and ENY2 are recruited into TFTC/STAGA by ATXN7L3 ( Figure 2 D)."

sparser
"Further, Pfam analysis of protein domain structures ( Finn et al., 2014 ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( Lan et al., 2015; Zhang et al., 2008b; Zhao e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Previous study has shown that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator SAGA complex to regulate global levels of H2B monoubiquitination ( xref )."

sparser
"We show that the ubiquitin protease USP22 forms a subcomplex with ATXN7L3 (ySgf11 homolog) and ENY2 (ySus1 homolog)."
2 | 2 1

sparser
"The association of USP22 and ENY2 in the same TFTC/STAGA module would therefore suggest that two activities, histone deubiquitination and mRNA export, may also be coregulated within this complex."

reach
"Further, Pfam analysis of protein domain structures confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar to that found in USP22, which is critical for USP22 interaction with ATXN7L3 and ENY2 and deubiquitination activity (XREF_FIG and XREF_SUPPLEMENTARY)."

No evidence text available

reach
"Further, Pfam analysis of protein domain structures (Finn et al., 2014) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar t[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

No evidence text available
CD274 affects USP22
2 | 2 11
2 | 2 11

sparser
"Now that USP22 could regulate PD-L1 protein level, we asked whether USP22 interacted with PD-L1."

reach
"XREF_BIBR, XREF_BIBR While USP22 interacts with PD-L1 and inhibits PD-L1 ubiquitination, this DUB binds and stabilizes CSN5, suggesting that its PD-L1-regulatory function may involve coordination with CSN5."

sparser
"Thus, we validated the interaction between USP22 and PD-L1."

sparser
"Furthermore, we confirmed the interaction between USP22 and PD-L1 both in HEK293FT and NSCLC cells."

reach
"Our data showed that USP22 interacted with PD-L1 and promoted its stability."

sparser
"In addition, USP22 could facilitated the interaction between CSN5 and PD-L1, and CSN5 promoted the interaction between USP22 and PD-L1."

sparser
"Our results showed that CSN5 enhanced the interaction between USP22 and PD-L1 (Fig.  xref a)."

sparser
"Our data showed that USP22 interacted with PD-L1 and promoted its stability."

sparser
"USP22 physically interacted with PD-L1."

No evidence text available
USP22 affects CDKN1A
| 13 1
USP22 decreases the amount of CDKN1A.
| 9
USP22 decreases the amount of CDKN1A. 9 / 9
| 9

reach
"GSK3beta- and USP22 dependent KDM1A stabilization is required for the demethylation of histone H3K4, thereby repressing BMP2, CDKN1A and GATA6 transcription, which results in cancer stem cell self-renewal and glioblastoma tumorigenesis."

reach
"USP22 has also been demonstrated to inhibit transcription of the p21 gene by deubiquitinating the transcriptional regulator, FBP1, leading to cell proliferation and tumorigenesis."

reach
"USP22-mediated deubiquitination of PTEN inhibits pancreatic cancer progression by inducing p21 expression."

reach
"Recent studies have demonstrated that USP22 can inhibit the transcription of the p21 gene by de-ubiquitinating the transcriptional regulator FBP1, leading to cell proliferation and tumorigenesis [XREF_BIBR]."

reach
"In MGC-803 cells and SGC-7901 cells, knockdown of USP22 and BMI1 both increased P21 expression and reduced the expression of CSC stemness genes of CD133 and SOX2."

reach
"USP22 also suppresses CDKN1A and p21 -locus expression by deubiquitinating its transcriptional repressor FBP1 (Atanassov and Dent, 2011), and acts as a negative regulator of the tumor suppressor p53 b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"We found that USP22 silencing in A549 and NCI-H460 cells increased the protein expression of p53, p21 and Bax, the key p53 signal molecules (XREF_FIG A), suggesting that p53 activation plays a role in USP22 silencing induced growth inhibition."

reach
"Furthermore, our results showed that USP22 deletion caused down -- regulation of cyclin D2 expression and up -- regulation of p15 and p21 expression."

reach
"We found that USP22 depletion inhibited the proliferation of the human GC cell lines MGC-803 and SGC-7901 cells and increased expression of P21, indicating cell cycle arrest [XREF_BIBR]."
USP22 increases the amount of CDKN1A.
| 2 1
USP22 increases the amount of CDKN1A. 3 / 3
| 2 1

reach
"We found USP22 silencing led to decreased expression of BMI1, as well as decreased P21 levels."

sparser
"USP22 induced p21 expression via PTEN in pancreatic cancer."

reach
"USP22 also play roles in cell cycle regulation, where depletion of USP22 increases the expression of p53 and p21, inhibits proliferation, and induces cell cycle arrest at G1 phase."
USP22 inhibits CDKN1A.
| 2
USP22 inhibits CDKN1A. 2 / 2
| 2

reach
"Hence USP22 silencing reduces the capacity of FBP1 to repress p21 (independently of TP53 status), which in turn inhibits CDKs to prevent the G1/S transition and resulting in G1 accumulation [XREF_BIBR]."

reach
"USP22 knockdown, using lentivirus delivered siRNA, increased the expression levels of cell cycle proteins P21 and P27, but reduced the levels of phosphorylated retinoblastoma protein, resulting in the inhibition of FaDu cell growth and proliferation."
USP22 affects TGFB1
| 9 2
USP22 increases the amount of TGFB1.
| 6
USP22 increases the amount of TGFB1. 4 / 5
| 4

reach
"And overexpression USP22 in A549 induced an increase of TGF-beta1 expression."

reach
"Ubiquitin specific protease 22 (USP22) reduces the degradation of sirtuin-1 and the expression of FN and TGF-beta1 in AGE treated GMCs, whereas depletion of USP22 promotes sirtuin-1 degradation and the expression of FN and TGF-beta1 in this cell model."

reach
"Moreover, USP22 may up-regulate TGF-beta1 expression."

reach
"Ubiquitin specific protease 22 (USP22) reduced Sirt1 ubiquitination and degradation and decreased FN and TGF-beta1 expression in GMCs under both basal and AGEs treated conditions."
Modified USP22 increases the amount of TGFB1. 2 / 2
| 2

reach
"In diabetic nephropathy, the increased expression of USP22 reduced the Sirt1 ubiquitination and degradation, and decreased fibronectin and TGF-beta1 expression in glomerular mesangial cells under both[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Furthermore, we have found overexpression of USP22 correlated with high TGF-beta1 expression in the lung ADC tissues.To determine whether USP22 expression in lung ADC cells induced EMT by changing the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 decreases the amount of TGFB1.
| 2
USP22 decreases the amount of TGFB1. 2 / 2
| 2

reach
"Ubiquitin specific protease 22 (USP22) reduces the degradation of sirtuin-1 and the expression of FN and TGF-beta1 in AGE treated GMCs, whereas depletion of USP22 promotes sirtuin-1 degradation and the expression of FN and TGF-beta1 in this cell model."

reach
"Ubiquitin specific protease 22 (USP22) reduced Sirt1 ubiquitination and degradation and decreased FN and TGF-beta1 expression in GMCs under both basal and AGEs treated conditions."
USP22 binds TGFB1.
| 1 1
| 1 1

sparser
"Therefore, our findings indicated that lung adenocarcinoma exhibiting nuclear USP22 expression was associated with increased TGF-β1, metastatic potential and poor survival outcomes."

reach
"The association between the USP22, TGF-beta1 and clinicopathologic parameters was tested using the chi-square tests."
USP22 activates TGFB1.
| 1
USP22 activates TGFB1. 1 / 2
| 1

sparser
"AP4 transcription is increased by TGF-β1 [ xref ], which, in turn, can be activated by USP22."
USP22 affects STING1
1 1 | 3 7
USP22 binds STING1.
1 | 7
1 | 7

sparser
"In line with this, USP22-283 induced ISG expression could be reversed as well in USP22-STING dKO HT-29 cells 284 (Figure 4H)."
| DOI

sparser
"E. Western blot 831 analysis of STING and USP22 expression levels in control-NHT, control-USP22 KO 832 #1 and #6, STING-NHT and STING-USP22 KO #1 and #6 double KO (dKO) HT-29 833 cells."
| DOI

sparser
"To investigate the significance of USP22 and the 326 resulting STING-mediated upregulation of type III IFN and ISG signaling for viral327 defense, the role of the USP22-STING axis was tested during SARSexpression of STING, compared to wild-type (WT) and NHT 332 CRISPR/Cas9 control Caco-2 cells (Figure 6A)."
| DOI

sparser
"288 289 USP22 negatively regulates STING activation and ubiquitination 290 The differential response to ISD, but not poly(I:C), and the reversal of the IFN signature 291 in USP22-STING dKO hIECs suggests an important role of USP22 in the control of 292 STING-induced type III IFN signaling."
| DOI

No evidence text available

sparser
"To confirm the role of STING in USP22-induced type III IFN 279 signaling, USP22-STING dKO HT-29 cells were generated (Figure 4G)."
| DOI

sparser
"Intriguingly, 351 USP22-STING dKO hIECs exhibit higher SARS-CoV-2 replication rates as well as the formation of more de novo infectious viral particles compared to USP22 inflammatory diseases and cancer 1,2 ."
| DOI

sparser
"F. Quantification of relative SARS-CoV-2 835 genome expression of SARS-CoV-2-infected control-NHT, control-USP22 KO #1 and 836 #6, STING-NHT and STING-USP22 KO #1 and #6 dKO HT-29 cells at 24 hpi."
| DOI
USP22 deubiquitinates STING1.
1 | 3
USP22 leads to the deubiquitination of STING1. 4 / 4
1 | 3

reach
"USP22 negatively regulates STING activation and ubiquitination."
| DOI

reach
"We furthermore demonstrate for the first time that in the absence of viral 421 infections or exogenous IFN, loss of USP22 expression resulted in basal and 2'3'-422 cGAMP-induced STING ubiquitination in hIECs."
| DOI

"USP22 removes K27-linked ubiquitination on STING through cooperation with USP13"

reach
"288 289 USP22 negatively regulates STING activation and ubiquitination 290 The differential response to ISD, but not poly(I:C), and the reversal of the IFN signature 291 in USP22-STING dKO hIECs suggests an important role of USP22 in the control of 292 STING-induced type III IFN signaling."
| DOI
USP22 affects RCAN1
3 | 5 2
USP22 binds RCAN1.
3 | 2 2
3 | 2 2

sparser
"Moreover, we found that RCAN1 was bound to USP22 in basal conditions, and interferon-α (IFN-α) treatment caused the dissociation of RCAN1 from USP22, which subsequently triggered RCAN1 ubiquitination and proteasome degradation."

reach
"Moreover, we found that RCAN1 was bound to USP22 in basal conditions, and interferon-alpha (IFN-alpha) treatment caused the dissociation of RCAN1 from USP22, which subsequently triggered RCAN1 ubiquitination and proteasome degradation."

No evidence text available

No evidence text available

No evidence text available

sparser
"In the present study, we have identified a novel interaction between USP22 and RCAN1 (RCAN1-1S) in the mammalian cells."

reach
"In the present study, we have identified a novel interaction between USP22 and RCAN1 (RCAN1-1S) in the mammalian cells."
USP22 activates RCAN1.
| 1
USP22 activates RCAN1. 1 / 3
| 1

reach
"In addition, the overexpression of USP22 caused the increase of RCAN1 protein stability."
USP22 ubiquitinates RCAN1.
| 1
USP22 leads to the ubiquitination of RCAN1. 1 / 1
| 1

reach
"Moreover, we found that RCAN1 was bound to USP22 in basal conditions, and interferon-alpha (IFN-alpha) treatment caused the dissociation of RCAN1 from USP22, which subsequently triggered RCAN1 ubiquitination and proteasome degradation."
USP22 increases the amount of RCAN1.
| 1
USP22 increases the amount of RCAN1. 1 / 1
| 1

reach
"Taken together, these results suggest that USP22 positively regulates RCAN1 levels, which would consequently affect diverse RCAN1 linked cellular processes, such as the inflammatory process involving the release of IFN-alpha."
USP22 affects EGFR
1 | 11
USP22 activates EGFR.
| 5
USP22 activates EGFR. 5 / 5
| 5

reach
"Of note, more EGFR colocalized with Rab11 in the PC9 cells with overexpression of USP22 than the control cells, which confirms that USP22 enhances EGFR recycling."

reach
"However, our finding on prevention of endocytosis mediated EGFR degradation by USP22 reveals one vital aspect of USP22 's diverse functions."

reach
"Our study suggests that USP22 antagonizes EGFR degradation and amplifies EGFR signaling activity to promote EGFR-TKIs resistance in EGFR mutated lung ADCs."

reach
"Thus, stabilization and activation of EGFR by USP22 are likely to be important factors in the mechanism underlying the oncogenicity and drug-resistance in EGFR-mutant lung ADCs."

reach
"We show here that overexpression of USP22 prevents EGFR down-regulation, while shRNA mediated silencing of USP22 enhances EGFR degradation."
USP22 deubiquitinates EGFR.
1 | 3
USP22 deubiquitinates EGFR. 4 / 4
1 | 3

"Additionally, USP22 sustained the activation of multiple EGFR downstream signaling pathways, including STAT3, AKT/mTOR and MEK/ERK pathways, in lung ADC cell lines H1975 and PC9."

reach
"In this model, late endosome localized USP22 deubiquitinates EGFR and impedes sorting of EGFR to the lysosome, thus sustaining the trafficking of EGFR to the plasma membrane (Figs. 6 and 9)."

reach
"Similarly, shRNA knockdown of USP22 resulted in accumulated Ubn-EGFR, which further confirmed that USP22 antagonizes EGFR ubiquitination."

reach
"Mechanistically, USP22 deubiquitinates EGFR localized on late endosomes, prevents ubiquitination mediated EGFR degradation and enhances recycling of EGFR after EGF stimulation."
USP22 inhibits EGFR.
| 3
USP22 inhibits EGFR. 3 / 3
| 3

reach
"We show here that overexpression of USP22 prevents EGFR down-regulation, while shRNA mediated silencing of USP22 enhances EGFR degradation."

reach
"Our current study demonstrates that USP22 promotes EGFR-TKIs resistance by preventing EGFR degradation in EGFR-mutant lung ADC."

reach
"USP22 promotes resistance to EGFR-TKIs by preventing ubiquitination mediated EGFR degradation in EGFR-mutant lung adenocarcinoma."
| 11

reach
"These results suggest that while USP22 promotes cell migration and invasion, loss of USP22 sensitizes EGFR mutant NSCLC cells to erlotinib in vitro."

reach
"Indeed, compared with control, we found that the USP22 knockdown cells grew significantly more slowly in H1650 (p < 0.05, Fig. 2 B) and the USP22 overexpression in A549 accelerated cell growth (p < 0.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The results showed cancer cell migration was significantly inhibited by knockdown of USP22 in H1650 (p < 0.05, Fig. 2 C)."

reach
"Our results also demonstrated that USP22 can increase cell migration and invasion abilities via EMT induction."

reach
"USP22 increases CRC cell migration and invasion by inducing EMT."

reach
"These results suggest that USP22 promotes in vitro GC cell migration and invasion."

reach
"Taken together, these results indicate that USP22 increases cell migration and invasion by inducing EMT by binding to the promoter of AP4 to activate its transcription."

reach
"These results indicate that USP22 increases CRC cell migration and invasion abilities by promoting EMT."

reach
"USP22 silencing suppresses in vitro GC cell migration and invasiveness."

reach
"Therefore, USP22 silencing impairs ATC cell migration and invasion by ablating EMT."
USP22 affects IRF3
| 11
| 11

sparser
"Interestingly, we found that the USP22(RR164/165AA) was still associated with IRF3 ( xref )."

sparser
"Because USP22-mediated virus-triggered signaling requires its enzyme activity and USP22 interacts with IRF3, we hypothesized that USP22 might catalyze deubiquitination of IRF3 and regulate the nuclear translocation of IRF3."

sparser
"USP22 is associated with IRF3 after viral infection."

sparser
"These data suggest that USP22 interacts with IRF3 in the cytoplasm after viral infection."

sparser
"Viral infection induced USP22-IRF3 association in the cytoplasm in a KPNA2-depedent manner, and knockdown or knockout of USP22 or KPNA2 impaired IRF3 nuclear translocation and expression of downstream genes after viral infection."

sparser
"We observed that USP22 interacted with IRF3 and phosphorylated IRF3 (pIRF3) in the cytoplasm but not in the nucleus after vesicular stomatitis virus (VSV) or HSV-1 infection in BMDCs ( xref )."

sparser
"In this context, we observed that IRF3(IL139/140AA), which is predominantly located in the nucleus, did not interact with USP22, and USP22(RR164/165AA) interacted with IRF3, as did wild-type USP22."

sparser
"USP22 interacted with IRF3 after viral infection in a KPNA2-dependent manner."

sparser
"Together with the observations that knockdown of KPNA2 impaired IRF3-USP22 associations after viral infection and that reconstitution of KPNA2 into USP22 knockout cells restored virus-induced nuclear translocation of IRF3 and expression of downstream genes, we concluded that USP22 promotes nuclear translocation of IRF3 primarily through deubiquitinating and stabilizing KPNA2."

sparser
"Such an intermediate protein should associate with both IRF3 and USP22 and promote virus-triggered signaling by facilitating the nuclear translocation of IRF3."
USP22 affects ATXN7
8 | 1 1
8 | 1

No evidence text available

reach
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC and STAGA."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
| 1

sparser
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC/STAGA ( Figure 1 D, lane 4)."

reach
"Owing to its relationship with the chemotherapeutic resistance of several types of human cancers (Glinsky, 2005), cyclin B1 may also mediate the USP22 induced MDR in HCC cells, which is valuable for future exploration."

reach
"These results confirmed the role of SIRT1 in USP22 induced MDR in HCC cells."

eidos
"] Our previous work revealed that USP22 was able to promote HCC stemness by a HIF1alpha / USP22 positive feedback loop and mediate multidrug resistance ( MDR ) by activating the SIRT1 / AKT / MRP1 pathway ."

reach
"XREF_BIBR Ubiquitin specific protease 22 (USP22) mediates the MDR of HCC via the SIRT1/AKT/MRP1 signaling pathway."

reach
"Simply put, USP22 may activate the SIRT1–AKT–MRP1 pathway and consequently promote MDR in human HCC cells (226)."

reach
"First, we defined SIRT1 as a significant mediator in USP22 driven MDR in HCC."

reach
"Together, these results indicate that USP22 could promote the MDR in HCC cells by activating the SIRT1/AKT/MRP1 pathway."

reach
"Taken together, the present study found that USP22 can promote the MDR in HCC cells via activating the SIRT1/AKT/MRP1 pathway."

reach
"Interestingly, we found that modulation of USP22 or SIRT1 could influence the intracellular ADR concentration, which might partly bridge the induction of MDR by USP22 and SIRT1 in HCC cells."
USP22 increases the amount of diphenylmethane-4,4'-diisocyanate.
| 2
| 2

reach
"Moreover, USP22 knockdown also decreases MDR related genes expression by inhibiting Akt phosphorylation, and USP22 knockdown mediated Smad4 up-regulation is crucial for Akt suppression."

reach
"USP22 knockdown decreased MDR related genes expression through up-regulation of Smad4 and suppression of Akt."
IRF3 affects USP22
| 11
| 11

sparser
"Interestingly, we found that the USP22(RR164/165AA) was still associated with IRF3 ( xref )."

sparser
"Because USP22-mediated virus-triggered signaling requires its enzyme activity and USP22 interacts with IRF3, we hypothesized that USP22 might catalyze deubiquitination of IRF3 and regulate the nuclear translocation of IRF3."

sparser
"USP22 is associated with IRF3 after viral infection."

sparser
"These data suggest that USP22 interacts with IRF3 in the cytoplasm after viral infection."

sparser
"Viral infection induced USP22-IRF3 association in the cytoplasm in a KPNA2-depedent manner, and knockdown or knockout of USP22 or KPNA2 impaired IRF3 nuclear translocation and expression of downstream genes after viral infection."

sparser
"We observed that USP22 interacted with IRF3 and phosphorylated IRF3 (pIRF3) in the cytoplasm but not in the nucleus after vesicular stomatitis virus (VSV) or HSV-1 infection in BMDCs ( xref )."

sparser
"In this context, we observed that IRF3(IL139/140AA), which is predominantly located in the nucleus, did not interact with USP22, and USP22(RR164/165AA) interacted with IRF3, as did wild-type USP22."

sparser
"USP22 interacted with IRF3 after viral infection in a KPNA2-dependent manner."

sparser
"Together with the observations that knockdown of KPNA2 impaired IRF3-USP22 associations after viral infection and that reconstitution of KPNA2 into USP22 knockout cells restored virus-induced nuclear translocation of IRF3 and expression of downstream genes, we concluded that USP22 promotes nuclear translocation of IRF3 primarily through deubiquitinating and stabilizing KPNA2."

sparser
"Such an intermediate protein should associate with both IRF3 and USP22 and promote virus-triggered signaling by facilitating the nuclear translocation of IRF3."
ALKBH5 affects USP22
| 1 10
ALKBH5 increases the amount of USP22.
| 6
ALKBH5 increases the amount of USP22. 6 / 6
| 6

reach
"Because ALKBH5 KD increased m A levels and significantly decreased USP22 mRNA steady-state levels, we performed mRNA stability analyses in scrambled siRNA and ALKBH5-silenced osteosarcoma cells."

reach
"ALKBH5 silencing led to significantly reduced expression of USP22 in 143B, U2OS, and OS-17 osteosarcoma cell lines (Fig. 4F; Supplementary Fig. S8D–S8G)."

reach
"Taken together, our data suggests that USP22 is highly sensitive to changes in m A levels and that ALKBH5 induces USP22 expression by maintaining an undermethylated state as increased methylation promotes accelerated decay of USP22 transcript in ALKBH5-depleted cells."

reach
"Methyl RNA immunoprecipitation sequencing analysis and functional studies showed that ALKBH5 mediates its protumorigenic function by regulating m 6 A levels of histone deubiquitinase USP22 and the ubiquitin ligase RNF40."

reach
"Me-RIP-seq analysis and functional studies showed that ALKBH5 mediates its pro-tumorigenic function by regulating m6A levels of histone deubiquitinase USP22 and the ubiquitin ligase RNF40."

reach
"Conversely, ALKBH5 overexpression increased USP22 expression in osteosarcoma cells (Fig. 4G; Supplementary Fig. S8H)."
ALKBH5 decreases the amount of USP22.
| 2
ALKBH5 decreases the amount of USP22. 2 / 2
| 2

reach
"Because ALKBH5 KD increased m A levels and significantly decreased USP22 mRNA steady-state levels, we performed mRNA stability analyses in scrambled siRNA and ALKBH5-silenced osteosarcoma cells."

reach
"Because ALKBH5 KD reduced USP22 expression, we wondered whether changes in ALKBH5 levels or activity affects H2A and H2B monoubiquitylation levels."
ALKBH5 activates USP22.
| 1 1
ALKBH5 activates USP22. 2 / 2
| 1 1

eidos
"Significance : RNA demethylase ALKBH5 upregulates USP22 and RNF40 to inhibit histone H2A ubiquitination and induces expression of key replication and DNA repair-associated genes , driving osteosarcoma progression ."

reach
"ALKBH5 mediates its protumorigenic function by inducing the stability of histone deubiquitinase ubiquitin specific peptidase 22 (USP22) and ubiquitin ligase RING finger protein 40 (RNF40) in a RNA methylation-dependent manner."
ALKBH5 inhibits USP22.
| 1
ALKBH5 inhibits USP22. 1 / 1
| 1

reach
"ALKBH5 KD significantly reduced USP22 mRNA stability compared with scrambled siRNA–treated cells (Supplementary Fig. S8I–S8J)."
| 6

reach
"Interestingly, our data showed that USP22 promotes the proliferation but inhibits the differentiation of NSCs in the dentate gyrus (DG)of the hippocampus soon after TBI."

reach
"Another study in mice showed that Usp22 negatively regulates neuronal differentiation in the mouse developing brain."

reach
"On the contrary, depletion of USP22 delays Hes1 oscillation and thereby, induces neuronal differentiation from neuronal progenitor stem cells ."

reach
"Moreover, USP22 depletion promotes the differentiation of NSCs, both in vitro and in vivo."

reach
"In contrast, USP22 overexpression inhibits NSC differentiation into neurons."

reach
"For instance, two histone directed DUBs, USP44 and USP22, are antagonistically regulated in their mRNA expression to ensure faithful stem cell differentiation [XREF_BIBR - XREF_BIBR]."
| 4

reach
"On the contrary, Usp22 overexpression leads to increased differentiation of ESCs into EBs even in the absence of stimuli that drives differentiation [XREF_BIBR]."

reach
"USP22 suppression also diminishes iNKT17 and iNKT1 differentiation but favors iNKT2 polarization without altering conventional T cell activation and differentiation."

reach
"In addition, Sussman RT, et al. have reported that USP22 promotes embryonic stem cell differentiation through transcriptional repression of Sex determining region Y-box 2 (Sox2) XREF_BIBR."

reach
"Knockdown of Usp22 shortened the half-life of Hes1, delayed its oscillation, and enhanced neuronal differentiation in mouse developing brain, whereas mis expression of Usp27x reduced neuronal differentiation."
USP22 affects SOX2
| 9
USP22 decreases the amount of SOX2.
| 8
USP22 decreases the amount of SOX2. 8 / 8
| 8

reach
"In mouse ES cells, Usp22 represses the transcription of the pluripotency factor Sox2, thereby promoting differentiation [XREF_BIBR]."

reach
"USP22 is known to bind to the promoter region of Sox2 and negatively regulates Sox2 transcription in embryonic stem cells (ESCs) 47."

reach
"Loss of Usp22 occupancy at the Sox2 locus is associated with elevated levels of H2Bub and increased transcription of Sox2."

reach
"In addition, USP22 occupies the Sox2 promoter and hydrolyzes mono-ubiquitin from ubiquitinated H2B (uH2B), and blocks transcription of the Sox2 locus."

reach
"DUBs that have been reported to control developmental processes through deubiquitylating H2B include USP44, which represses genes involved in lineage commitment during mESC maintenance [XREF_BIBR], and USP22, which specifically inhibits expression of the pluripotency factor SOX2 during hESC differentiation [XREF_BIBR]."

reach
"USP22 has been found to be located directly on the Sox2 promoter and catalyzes deubiquitination of H2B and attenuates Sox2 transcription."

reach
"USP22 is located directly on the Sox2 promoter and negatively regulates Sox2 transcription in ESCs [XREF_BIBR]."

reach
"In the recent study by Sussman et al., USP22 was shown to repress the expression of the Sox2 locus that encodes one of the core transcriptional regulators of ES-cell pluripotency (Sussman et al., 2013[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 inhibits SOX2.
| 1
USP22 inhibits SOX2. 1 / 2
| 1

reach
"Moreover they found USP22 represses the SOX2 promoter in order to control the embryonic stem cell transition from self-renewal to differentiation [XREF_BIBR] Therefore, not only is SOX2 an essential stem cell marker but its suppression is mandatory for cellular differentiation."
SP1 affects USP22
| 1 2 4
SP1 binds USP22.
| 4
| 4

sparser
"Results showed that Sp1 binds to the USP22 promoter in fibroblasts, suggesting that Sp1-DNA interaction may be required for USP22 repression."

sparser
"For example, SP1 and protein kinase A/cAMP response element-binding protein could bind to the USP22 promoter to suppress or promote USP22 transcription, respectively ( xref , xref )."

sparser
"Immunoprecipitation of cross-linked chromatin from HFL1 cells with an anti-Sp1 antibody followed by PCR amplification of the region (the sequence between-210 and +52) confirmed that the endogenous Sp1 protein does bind to this region of the USP22 promoter in HFL1 ( xref )."

sparser
"Interaction between Sp1 and the USP22 Promoter."
SP1 inhibits USP22.
| 1 1
SP1 inhibits USP22. 2 / 3
| 1 1

eidos
"In summary , our results demonstrate that USP22 expression is promoted by AP2 and c-Myc and is suppressed by SP1 and ATF3 at the transcriptional level ."

reach
"In contrast, knockdown of Sp1 enhanced USP22 promoter activity and mRNA levels."
SP1 decreases the amount of USP22.
| 1
SP1 decreases the amount of USP22. 1 / 3
| 1

reach
"For example, SP1 and protein kinase A/cAMP response element binding protein could bind to the USP22 promoter to suppress or promote USP22 transcription, respectively."
KDM1A affects USP22
| 4 4
KDM1A binds USP22.
| 4 3
| 4 3

sparser
"Using a series of KDM1A deletion mutants, we found that KDM1A’s AOL domain was required for KDM1A’s binding with USP22 ( xref )."

reach
"Moreover, GSK3beta knockdown in GSC11 cells attenuated the interaction between endogenous USP22 and KDM1A (XREF_FIG), which was confirmed in 293T cells by transfection of GSK3beta-KD as compared with GSK3beta-CA (XREF_SUPPLEMENTARY)."

reach
"The target relationship of USP22 and miR-362-3p as well as the interaction of USP22 and LSD1 in RB was verified."

sparser
"The target relationship of USP22 and miR-362-3p as well as the interaction of USP22 and LSD1 in RB was verified."

sparser
"Moreover, GSK3β knockdown in GSC11 cells attenuated the interaction between endogenous USP22 and KDM1A ( xref ), which was confirmed in 293T cells by transfection of GSK3β-KD as compared with GSK3β-CA ( xref )."

reach
"Using a series of KDM1A deletion mutants, we found that KDM1A 's AOL domain was required for KDM1A 's binding with USP22 (XREF_FIG)."

reach
"Furthermore, KDM1A S683A significantly decreased the interaction between USP22 and KDM1A in the presence of GSK3beta-CA (XREF_FIG)."
KDM1A ubiquitinates USP22.
| 1
KDM1A ubiquitinates USP22. 1 / 1
| 1

sparser
"However, of those four DUBs, only USP22 substantially decreased KDM1A ubiquitination ( xref )."
ENY2 affects ATXN7L3
| 10
| 10

sparser
"Cotransfection and coimmunoprecipitation experiments revealed that the ATXN7L3 ZnF-Sgf11 domain alone is able to interact with both ENY2 and USP22 as efficiently as the full-length ATXN7L3 (see Figur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Similarly, USP22, the human homolog of Ubp8, is bound to the STAGA complex through interactions with ATXN7L3 and ENY2, which are homologs of Sgf11 and Sus1, respectively ( xref )."

sparser
"The SAGA DUB module is highly conserved both in subunit composition and structural organization ( xref ; xref ; xref ; xref ; xref ; xref ), The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adapter proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( xref ; xref ; xref ), and a fourth protein, ATXN7 (Sgf73), anchors the DUB module to the larger SAGA complex."

sparser
"It has been reported that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator Spt-Ada-Gcn5-acetyltransferase (SAGA) complex to regulate global levels of H2B monoubiquitination, thereby promoting antibody class switch recombination by facilitating nonhomologous end joining ( xref ; xref ; xref )."

sparser
"Further, Pfam analysis of protein domain structures ( xref ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar to that found in USP22, which is critical for USP22 interaction with ATXN7L3 and ENY2 and deubiquitination activity ( xref and xref ) ( xref )."

sparser
"These results together suggest that ATXN7L3, USP22, and ENY2 form a stable subcomplex and that USP22 and ENY2 are recruited into TFTC/STAGA by ATXN7L3 ( Figure 2 D)."

sparser
"Further, Pfam analysis of protein domain structures ( Finn et al., 2014 ) confirmed that in addition to the catalytic UCH domain, both USP27X and USP51 have an N-terminal Znf-UBP domain highly similar[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) ( Lan et al., 2015; Zhang et al., 2008b; Zhao e[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Previous study has shown that USP22 interacts with ENY2 and ATXN7L3 and forms the transcriptional coactivator SAGA complex to regulate global levels of H2B monoubiquitination ( xref )."

sparser
"We show that the ubiquitin protease USP22 forms a subcomplex with ATXN7L3 (ySgf11 homolog) and ENY2 (ySus1 homolog)."
USP22 affects Ubiquitin
| 9
USP22 inhibits Ubiquitin.
| 7
| 7

reach
"Increasing evidence links deregulation of the ubiquitin specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group of tumor types, but its specificity and underlying mechanisms of action are not well defined."

reach
"Moreover, the study of the corresponding mechanism by which HULC upregulated COX-2 showed that HULC enhanced the level of ubiquitin specific peptidase 22 (USP22), which decreased ubiquitin mediated degradation of COX-2 protein by removing the conjugated polyubiquitin chains from COX-2 and finally stabilized COX2 protein."

reach
"It was also indicated that lncRNA HULC could up-regulate expression of ubiquitin-specific peptidase 22 (USP22) and reduce the ubiquitin-mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chain of Sirt1 [135]."

reach
"In liver cancer, upregulation of lncRNA HULC activates autophagy by increasing the expression of ubiquitin specific peptidase 22 (USP22) which in turn prevents the ubiquitin mediated degradation of silent information regulator 1 (SIRT1) by removing the conjugated polyubiquitin chains from SIRT1."

reach
"On the contrary, the deubiqutinase USP22 antagonizes the ubiquitin ligase complex RNF20/40 on H2B monoubiquitination."

reach
"It belongs to the DUB subset of Machado–Joseph disease (MJD) proteic domain-containing peptidases with Atxn3 (a.k.a. MJD1 and SCA3), encoded by the gene mutated in MJD, also termed type-3 spinocerebellar ataxia (SCA3), and Josephin domain-containing DUbs JosD1 and JosD2 (Table 1.7).27Aggregates formed by polyglutamine-expanded ataxin-7 sequester ubiquitin-specific peptidase USP22 that cannot then fulfill its deubiquitinating function in the SAGA complex, causing cytotoxicity and neurodegeneration [109]."
| PMC

reach
"HULC is overexpressed in HCC as it promotes growth in cancer cells through enhancing ubiquitin specific peptidase 22 (USP22) which reduces ubiquitin mediated degradation of COX-2 protein hence stabilizing and upregulating COX-2 protein [XREF_BIBR]."
USP22 activates Ubiquitin.
| 2
| 2

reach
"Interestingly, the human and fly SAGA complexes possess a module that houses ubiquitin hydrolase activity mediated by the USP22 (human) and Nonstop (fly) proteins."

reach
"As suspected from its domain structure, USP22 is able to hydrolyze a ubiquitin linkage from histone H2B in vitro and endogenous USP22 contributes ubiquitin hydrolase activity to the hSAGA complex."
USP22 affects USP22
| 8
USP22 decreases the amount of USP22.
| 3
USP22 decreases the amount of USP22. 3 / 4
| 3

reach
"USP22 siRNA transfection (58 nM) for 24 h was observed to significantly reduce expression of USP22 mRNA and protein in U87 and U251 cells (XREF_FIG)."

reach
"The results of western blot analysis showed that USP22R restored the levels of USP22 and COX-2 downregulated by USP22 siRNA."

reach
"XREF_FIG, USP22 specific siRNA effectively inhibited USP22 gene transcription and protein expression."
USP22 inhibits USP22.
| 3
USP22 inhibits USP22. 3 / 3
| 3

reach
"However, the increase in SIRT1 levels enhances its deacetylation activity, which in turn, deacetylates USP22 and other SAGA components, thereby decreasing the enzymatic activity of USP22 ."

reach
"Lastly, ubiquitylation of USP22 mediated by the anaphase promoter complex and cyclosome (APC/C) induces USP22 protein degradation during the cell cycle [XREF_BIBR]."

reach
"Supporting the regulation of USP22 by m A modification, knockdown of the methyltransferase METTL3 increased USP22 expression in ALKBH5-silenced 143B cells (Fig. 4H; Supplementary Fig. S9A)."
USP22 activates USP22.
| 2
USP22 activates USP22. 2 / 2
| 2

reach
"Phosphorylation of USP22 at T147 and S237 by cyclin dependent kinase 1 (CDK1) was shown to activate USP22 to deubiquitylate cyclin B1."

reach
"Interestingly, USP22 activity is regulated by CDK1, which catalyzes USP22 phosphorylation to elevate USP22 ability in CCNB1 deubiquitination and stabilization."
USP22 affects Histone
| 9
USP22 deubiquitinates Histone.
| 8
USP22 deubiquitinates Histone-H2A. 4 / 4
| 4

reach
"As a subunit of hSAGA, USP22 participates in the deubiquitination of histones H2A and H2B and the acetylation of histone H4 to regulate gene transcription and expression."

reach
"USP22 was initially reported to promote deubiquitylation of histones H2A and H2B, leading to transcription activation."

reach
"Several DUBs have been implicated in histone deubiquitination, including USP3, USP12, USP22, and USP46, which deubiquitinate both histones H2A and histones H2B [XREF_BIBR]."

reach
"As we discussed previously, USP22 is a component of a transcriptional activator complex SAGA and can deubiquitinate histones H2A and H2B, as well as several other substrates (Zhang et al., 2008a, b)."
USP22 deubiquitinates Histone. 4 / 4
| 4

reach
"USP22 also deubiquitinates non histone proteins, including telomeric repeat binding factor 1 (TRF1), sirtuin 1 (SIRT1), cyclin B1 and others, leading to protein stabilization by preventing proteasome mediated degradation."

reach
"In addition, certain non histone proteins such as sirtuin 1 (Sirt1) and fructose-bisphosphatase 1 (FBP1) could be deubiquitinated by USP22."

reach
"USP22 deubiquitylates histone and non histone substrates and has been associated with cancer progression and spinocerebellar ataxia."

reach
"USP22 deubiquitinates histone H2Bub and H2Aub."
USP22 increases the amount of Histone.
| 1
USP22 increases the amount of Histone. 1 / 1
| 1

reach
"USP22 induces the occurrence and development of LUAD by promoting the expression of H2AFX histone."
PTGS2 affects USP22
4 | 2 3
4 | 2 3

No evidence text available

No evidence text available

reach
"As shown in Fig. 2 C, USP22 was pulled down together with COX-2 but not with COX-1, confirming the specificity of the interaction between USP22 and COX-2."

reach
"To verify the direct interaction between USP22 and COX-2, recombinant USP22 was incubated with His tagged COX-2 or COX-1 and proteins were isolated by affinity chromatography."

sparser
"To verify the direct interaction between USP22 and COX-2, recombinant USP22 was incubated with His-tagged COX-2 or COX-1 and proteins were isolated by affinity chromatography."

sparser
"To examine the potential interaction between USP22 and COX-2, A549 cells were transfected with vectors expressing USP22 and Myc-tagged COX-2 and cell lysates were immunoprecipitated against anti-Myc [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As shown in C, USP22 was pulled down together with COX-2 but not with COX-1, confirming the specificity of the interaction between USP22 and COX-2."

No evidence text available

No evidence text available
End3 affects USP22
| 2 6
| 2 6

reach
"This raises the hypothesis that once USP22 associates with SAGA and GCN5, it may oppose telomere recombination in APBs by promoting the binding of POT1 to telomeres via TRF1, thereby inhibiting ATR activation."

sparser
"GCN5 is required for the association of SAGA with USP22, which is the component of its deubiquitination module, and the subsequent USP22-mediated deubiquitination of TRF1, which inhibits TRF1 degradation by proteasomes, thereby preventing signalling associated with telomere DNA damage and protecting telomeres from fusions."

sparser
"GCN5 has been shown to support the association of USP22 with the SAGA complex."

sparser
"USP22 forms part of the SAGA complex and requires the participation of cofactors like ATXN7L3 and ENY2 to deubiquitinate H2B, while USP27X functions independently of SAGA but also needs ATXN7L3 and ENY2 to act on H2B [ xref ]."

sparser
"On the contrary, as a part of the SAGA complex, USP22, by deubiqitinating TRF1, restores its protein level and thereby maintains telomeric length."

reach
"Although this shows USP22 can bind both PALB2 and SAGA it does not delineate whether these are two separate populations or whether USP22 can interact with all of these components including PALB2 at the same time."

sparser
"GCN5 was found to be required for USP22 to properly associate with the SAGA complex and to be able to deubiquitinate TRF1 and prevent its turnover ( xref )."

sparser
"Like in Drosophila , USP22 associates with human SAGA, and is recruited to specific genes by activators such as the MYC oncoprotein for transcription [ xref ]."
USP22 affects XRCC6
| 8
USP22 deacetylates XRCC6.
| 6
USP22 deacetylates XRCC6. 6 / 6
| 6

reach
"(2) USP22 decreases the acetylation of Ku70 by stabilizing Sirt1, thus inhibiting Bax mediated apoptosis and inducing cisplatin resistance."

reach
"In addition, USP22 could also decrease the acetylation of Ku70 by stabilizing the expression of Sirt1, thus inhibiting Bax mediated apoptosis and contributing to cisplatin resistance."

reach
"These results suggest that USP22 decreases the acetylation of Ku70 by stabilizing Sirt1, thus inhibiting Bax mediated apoptosis and inducing cisplatin resistance."

reach
"USP22 Decreases the Acetylation of Ku70 by Stabilizing Sirt1, thus Inhibiting Bax Mediated Apoptosis and Inducing Cisplatin Resistance."

reach
"In addition, USP22 decreases the acetylation of Ku70 by stabilizing Sirt1, thus inhibiting Bax mediated apoptosis and inducing cisplatin resistance."

reach
"In addition, USP22 was shown to decrease the acetylation of Ku70 by stabilizing SIRT11 via deubiquitination."
USP22 acetylates XRCC6.
| 2
USP22 acetylates XRCC6. 2 / 2
| 2

reach
"In addition, USP22 was shown to decrease the acetylation of Ku70 by stabilizing SIRT11 via deubiquitination."

reach
"To verify whether USP22 mediates cisplatin resistance by regulating Ku70 acetylation via Sirt1, we inhibited the expression of Sirt1 while overexpressing USP22."
| 3 3 1
USP22 activates Carcinogenesis.
| 3 3
| 3 3

eidos
"In addition , we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis , however , this tumorigenicity is suppressed by inhibiting the expression of PPARgamma , ACLY , or ACC in in vivo tumorigenesis experiments ."

eidos
"Evidently , HnRNPA1 is a downstream transcription regulator of c-Myc ( proto-oncogene ) whereas USP22 positively regulates c-Myc stability and promotes tumorigenesis [ 35,36 ] ."

eidos
"Further , USP22 is shown to facilitate cell-cycle progression and colorectal tumorigenesis by targeting CCNB1 while in glioblastoma , USP22 promotes tumorigenesis via stabilizing KDM1A [ 89,90 ] ."

reach
"Together, these results support that USP22 promotes CRC cell proliferation and tumorigenesis by stabilizing FASN."

reach
"Together, these results suggest that FASN is stabilized by USP22 in colorectal cancer, and the dysregulated USP22/FASN axis is a important driver for tumorigenesis."

reach
"In addition, we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis, however, this tumorigenicity is suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vivo tumorigenesis experiments."
USP22 inhibits Carcinogenesis.
| 1

sparser
"Therefore, our results from the mouse xenograft model demonstrate that USP22 silencing inhibits NSCLC tumorigenesis in vivo through regulating the MDMX–p53 pathway."
USP22 affects COPS5
| 2 6
USP22 binds COPS5.
| 1 6
| 1 6

sparser
"Taken together, USP22 interacted with CSN5 and stabilized CSN5 protein through its deubiquitination activity."

sparser
"USP22 interacted with CSN5 and deubiquitinated CSN5."

sparser
"As expected, USP22 interacted with CSN5 exogenously and endogenously (Fig.  xref a, Fig. xref b)."

sparser
"Since CSN5 bound to PD-L1 [ xref ], we wondered if USP22 interacted with CSN5 physically."

reach
"Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination."

sparser
"Mechanistically USP22 interacts with CSN5 and stabilizes CSN5 in part through deubiquitination, which further inhibits the degradation of PD-L1 in cells [ xref ]."

sparser
"Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination."
USP22 deubiquitinates COPS5.
| 1
USP22 deubiquitinates COPS5. 1 / 1
| 1

reach
"USP22 can deubiquitinate PD-L1 itself or CSN5 for their stabilization [233] (Figure 3)."
| PMC
USP22 affects AR-V7
| 8
USP22 binds AR-V7.
| 3
USP22 binds AR-V7. 3 / 3
| 3

reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."

reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."

reach
"We confirmed the endogenous interaction between AR-V7 and USP22."
USP22 inhibits AR-V7.
| 2
USP22 inhibits AR-V7. 2 / 2
| 2

reach
"Furthermore, the overexpression of USP14/USP22 reversed the degradation of AR-V7 induced by nobiletin to a certain extent, and partly recovered the viability of CRPC cells."

reach
"Further studies on molecular biology revealed that nobiletin selectively induced AR-V7 degradation by inhibiting the interaction of AR-V7 with deubiquitylating enzymes (DUBs), including the ubiquitin-specific protease 14 (USP14) and 22 (USP22)."
USP22 activates AR-V7.
| 2
USP22 activates AR-V7. 2 / 2
| 2

reach
"Furthermore, CHX-tracking assay showed that USP22 depletion significantly decreased the half-life of AR-V7."

reach
"In reverse, overexpression of USP22 slowed down the attenuation of AR-V7 (Fig. 5E–H)."
USP22 increases the amount of AR-V7.
| 1
USP22 increases the amount of AR-V7. 1 / 1
| 1

reach
"To our expectation, the results showed that the knockdown of USP22 decreased AR-V7 expression."
| 6

reach
"As shown in Figure XREF_FIG, USP22 activates AP4 expression during EMT induction."

reach
"In summary, USP22 induces EMT by activating AP4 transcription to enhance CRC cell migration and invasion."

reach
"USP22 induces EMT by activating AP4 transcription."

reach
"The key findings of the study are as follows : (i) USP22 enhances CRC cell migration and invasion by inducing EMT, (ii) USP22 directly increases AP4 transcription to induce EMT and promote CRC cell metastasis to the lungs in vivo, and (iii) USP22 and AP4 overexpression is related to CRC progression and liver metastasis and poor outcomes in CRC patients."

reach
"Moreover, USP22 up-regulation induces EMT by directly increasing AP4 transcription, resulting in CRC cell metastasis to the lungs in vivo."

reach
"USP22 up-regulation enhances CRC cell migration and invasion and EMT related marker and AP4 expression, but these effects are partly blocked by AP4 knockdown."

reach
"The association between USP22 and AP4 and liver, but not lymph node, metastasis may be due to these proteins driving blood stream, but not lymphatic, metastasis of CRC cells."

reach
"Consistent with the above results, ChIP analysis revealed that USP22 binds the promoter region of AP4."
STING1 affects USP22
1 | 7
1 | 7

sparser
"In line with this, USP22-283 induced ISG expression could be reversed as well in USP22-STING dKO HT-29 cells 284 (Figure 4H)."
| DOI

sparser
"E. Western blot 831 analysis of STING and USP22 expression levels in control-NHT, control-USP22 KO 832 #1 and #6, STING-NHT and STING-USP22 KO #1 and #6 double KO (dKO) HT-29 833 cells."
| DOI

sparser
"To investigate the significance of USP22 and the 326 resulting STING-mediated upregulation of type III IFN and ISG signaling for viral327 defense, the role of the USP22-STING axis was tested during SARSexpression of STING, compared to wild-type (WT) and NHT 332 CRISPR/Cas9 control Caco-2 cells (Figure 6A)."
| DOI

sparser
"288 289 USP22 negatively regulates STING activation and ubiquitination 290 The differential response to ISD, but not poly(I:C), and the reversal of the IFN signature 291 in USP22-STING dKO hIECs suggests an important role of USP22 in the control of 292 STING-induced type III IFN signaling."
| DOI

No evidence text available

sparser
"To confirm the role of STING in USP22-induced type III IFN 279 signaling, USP22-STING dKO HT-29 cells were generated (Figure 4G)."
| DOI

sparser
"Intriguingly, 351 USP22-STING dKO hIECs exhibit higher SARS-CoV-2 replication rates as well as the formation of more de novo infectious viral particles compared to USP22 inflammatory diseases and cancer 1,2 ."
| DOI

sparser
"F. Quantification of relative SARS-CoV-2 835 genome expression of SARS-CoV-2-infected control-NHT, control-USP22 KO #1 and 836 #6, STING-NHT and STING-USP22 KO #1 and #6 dKO HT-29 cells at 24 hpi."
| DOI
AR affects USP22
| 3 5
| 3 3

reach
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"No significant association of AR and USP22 with chromatin at an intergenic region could be detected, and the amount of histone H3 at KLK2 promoter remained constant, further demonstrating specificit[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Subsequent immunoprecipitation also confirmed the association between AR and USP22 in vitro, which is consistent with the result of previous studies (Fig. 3I)."

reach
"Cotransfection in HEK293T cells and coimmunoprecipitation experiments revealed that AR interacted with ATXN7L3 in a ligand dependent manner, similarly to GCN5, while interaction between AR and USP22 w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Cotransfection in HEK293T cells and coimmunoprecipitation experiments revealed that AR interacted with ATXN7L3 in a ligand-dependent manner, similarly to GCN5, while interaction between AR and USP22 w[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"As AR and USP22 interacted in vivo, we next tested whether AR could be a substrate of the TFTC/STAGA deubiquitination activity."
USP22 binds ATXN7L3 and AR. 2 / 2
| 2

sparser
"To further investigate this hypothesis, we analyzed putative interactions of USP22 or ATXN7L3 with AR in mammalian cells."

sparser
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR-dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 affects autophagy
| 6
| 6

reach
"USP22 induced autophagy was also found to enhance cell proliferation and resistance to starvation and chemotherapeutic drugs in Panc-1 cells, therefore expressing an overall effect that promotes cell survival."

reach
"In addition, in a pancreatic cancer cell line (Panc-1), USP22 overexpression stimulates autophagy through the ERK1/2 pathway and hereby promotes resistance to gemcitabine treatment [XREF_BIBR]."

reach
"USP22 upregulation may thus inhibit apoptosis and stimulate autophagy in response to treatment with DNA damaging agents or targeted inhibitors to promote resistance to chemotherapy in cancer patients."

reach
"Beyond regulating apoptosis, the USP22 and SIRT1 pathway may also modulate autophagy."

reach
"USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy."

reach
"Taken together, these findings reveal a potential mechanism underlying the chemoresistance of PC cells mediated by the regulation of USP22 mediated autophagy by miR-29c, suggesting potential targets and therapeutic strategies in PC."
USP22 affects RAS
| 7
USP22 activates RAS.
| 6
USP22 activates RAS. 6 / 6
| 6

reach
"SOS1 silencing also attenuated the USP22-induced activation of RAS/ERK and PI3K/AKT signaling both in vitro and in vivo."

reach
"Chromatin immunoprecipitation revealed that the overexpression of USP22 induced the upregulation of RAS activator son of sevenless 1 (SOS1) in SGC7901 cells."

reach
"In this study, using a ChIP assay, we demonstrated, for the first time, that the overexpression of USP22 induced the upregulation of RAS activator SOS1 in SGC7901 cells."

reach
"USP22 overexpression in gastric cancer cells induces the upregulation of SOS1 and activation of the RAS/ERK and PI3K/AKT pathways."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS and ERK and PI3K and AKT pathways in SGC7901 cells and xenograft tumor tissues."
USP22 increases the amount of RAS.
| 1
USP22 increases the amount of RAS. 1 / 1
| 1

reach
"Indeed, USP22 overexpression induces significant elevations in protein levels of SOS1, RAS, p-ERK, p-PI3K, and p-AKT in both SGC7901 cells and tumors."
USP22 affects PI3K
| 7
USP22 activates PI3K.
| 5
USP22 activates PI3K. 5 / 5
| 5

reach
"Previous study also showed that USP22 promotes cell cycle progression by positively regulating the PI3K and Akt pathway [XREF_BIBR]."

reach
"USP22 overexpression in gastric cancer cells induces the upregulation of SOS1 and activation of the RAS/ERK and PI3K/AKT pathways."

reach
"These results suggest that USP22 downregulation inhibits OS cells by suppressing the PI3K and Akt pathway."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS and ERK and PI3K and AKT pathways in SGC7901 cells and xenograft tumor tissues."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues."
USP22 inhibits PI3K.
| 1
USP22 inhibits PI3K. 1 / 1
| 1

reach
"Downregulation of USP22 Inhibited the Activation of PI3K and Akt Signaling Pathway."
USP22 decreases the amount of PI3K.
| 1
USP22 decreases the amount of phosphorylated PI3K. 1 / 1
| 1

reach
"The results showed that USP22 downregulation remarkably decreased the protein expression of p-PI3K and p-Akt without change in the total protein levels of PI3K and Akt."
USP22 affects Cyclin
| 7
USP22 activates Cyclin.
| 3
USP22 activates Cyclin. 3 / 3
| 3

reach
"Hence, USP22 overexpression was associated with reduced p21 and p27 levels and increased abundance of Cyclin D1, CDK4 and CDK6, which collectively form a complex that promotes G1 progression [XREF_BIBR]."

reach
"In addition, Usp22 promotes CRC by stabilizing cyclin B1."

reach
"An in vitro study showed that the upregulation of USP22 mediated the enhanced expression of BMI1 and Cyclin D2, and was responsible for increased cell proliferation and the metastatic behavior of colon cancer cells ."
USP22 phosphorylates Cyclin.
| 2
USP22 leads to the phosphorylation of Cyclin. 2 / 2
| 2

reach
"In vitro assays showed that USP22 depletion suppressed ATC cell survival and proliferation by decreasing Rb phosphorylation and cyclin D2, inactivating Akt, and simultaneously upregulating Rb; USP22 silencing restrained cell migration and invasion by inhibiting epithelial-mesenchymal transition; USP22 knockdown promoted mitochondrion- mediated and caspase dependent apoptosis by upregulating Bax and Bid and promoting caspase-3 activation."

reach
"Molecular analysis of the tumor tissues showed that USP22 knockdown reduced the levels of cyclin D2, Akt phosphorylation, vimentin, and Bcl-2, whereas upregulated the expressions of E-cadherin, Bax, and cleaved (cl)-caspase-3, which confirmed in vitro findings."
USP22 inhibits Cyclin.
| 1
USP22 inhibits Cyclin. 1 / 1
| 1

reach
"Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora-B, Survivin and Cyclin B, together with the upregulation of cyclin dependent kinase inhibitor 1A (p21)."
USP22 dephosphorylates Cyclin.
| 1
USP22 leads to the dephosphorylation of Cyclin. 1 / 1
| 1

reach
"Mechanistically, we found that USP22 depletion dramatically decreased Akt phosphorylation and cyclin D2 expression."
RCAN1 affects USP22
3 | 2 2
3 | 2 2

sparser
"Moreover, we found that RCAN1 was bound to USP22 in basal conditions, and interferon-α (IFN-α) treatment caused the dissociation of RCAN1 from USP22, which subsequently triggered RCAN1 ubiquitination and proteasome degradation."

reach
"Moreover, we found that RCAN1 was bound to USP22 in basal conditions, and interferon-alpha (IFN-alpha) treatment caused the dissociation of RCAN1 from USP22, which subsequently triggered RCAN1 ubiquitination and proteasome degradation."

No evidence text available

No evidence text available

No evidence text available

sparser
"In the present study, we have identified a novel interaction between USP22 and RCAN1 (RCAN1-1S) in the mammalian cells."

reach
"In the present study, we have identified a novel interaction between USP22 and RCAN1 (RCAN1-1S) in the mammalian cells."
HULC affects USP22
| 1 5
HULC activates USP22.
| 1 4
HULC activates USP22. 4 / 4
| 4

reach
"XREF_BIBR Similarly, HULC is able to stabilize silent information regulator 1 (Sirt1) protein in hepatocellular carcinoma cells because HULC can upregulate ubiquitin specific peptidase 22 (USP22), and suppress ubiquitin mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1, XREF_BIBR leading to autophagy and chemoresistance."

reach
"HULC upregulated ubiquitin specific peptidase 22 (USP22), leading to the decrease of ubiquitin mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1 [XREF_BIBR]."

reach
"The investigation for the corresponding mechanism by which HULC stabilized Sirt1 revealed that HULC upregulated ubiquitin specific peptidase 22 (USP22), leading to the decrease of ubiquitin mediated degradation of Sirt1 protein by removing the conjugated polyubiquitin chains from Sirt1."

reach
"HULC downregulates the abovementioned miRs and strongly upregulates USP22."
HULC activates USP22. 1 / 2
| 1

eidos
"HULC upregulated ubiquitin-specific peptidase 22 ( USP22 ) , thus abrogating ubiquitin-mediated degradation of SIRT1 [ 35 ] ."
HULC inhibits USP22.
| 1
HULC inhibits USP22. 1 / 1
| 1

reach
"MiR-6825-5p, miR-6845-5p, and miR-6886-3p were down-regulated by HULC, resulting in the elevation of Sirt1, USP22, and protective autophagy, thus attenuating the sensitivity of HCC cells to chemotherapeutic agents [82]."
COPS5 affects USP22
| 1 6
| 1 6

sparser
"Taken together, USP22 interacted with CSN5 and stabilized CSN5 protein through its deubiquitination activity."

sparser
"USP22 interacted with CSN5 and deubiquitinated CSN5."

sparser
"As expected, USP22 interacted with CSN5 exogenously and endogenously (Fig.  xref a, Fig. xref b)."

sparser
"Since CSN5 bound to PD-L1 [ xref ], we wondered if USP22 interacted with CSN5 physically."

reach
"Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination."

sparser
"Mechanistically USP22 interacts with CSN5 and stabilizes CSN5 in part through deubiquitination, which further inhibits the degradation of PD-L1 in cells [ xref ]."

sparser
"Moreover, USP22 also interacted with CSN5 and stabilized CSN5 through deubiquitination."
USP22 affects miR-34b
| 6
USP22 activates miR-34b.
| 4
USP22 activates miR-34b. 4 / 4
| 4

reach
"MTT (XREF_FIG), cell cycle (XREF_FIG), and colony formation analyses (XREF_FIG) show that overexpression of USP22 can significantly attenuate the suppressive effect of miR-34b."

reach
"To confirm that USP22 is a direct target of miR-34b, we cloned the 3 '-UTR of USP22 into a reporter plasmid downstream of the luciferase gene."

reach
"Overexpression of USP22 attenuates the inhibitory effect of miR-34b on NPCcell proliferation."

reach
"Overexpression of USP22 attenuates the inhibitory effect of miR-34b on NPC cell viability and proliferation, thus confirming our hypothesis that miR-34b inhibits NPC proliferation by downregulating USP22."
USP22 inhibits miR-34b.
| 2
USP22 inhibits miR-34b. 2 / 2
| 2

reach
"Restoration of USP22 expression could reverse the effect of miR-34b on NPC cell viability and proliferation."

reach
"Notably, the overexpression of USP22 rescued the inhibitory effect of miR-34b on NPC, demonstrating that miR-34b suppresses the proliferation of NPC by targeting USP22."
| 1 3

reach
"Taken together, the findings of the present study have demonstrated for the first time that USP22 inhibition attenuates high glucose induced podocyte injuries and inflammation."

reach
"Silencing of USP22 suppressed ROS production and inflammation while inhibition of USP14 reduced the accumulation of oxidized proteins."

reach
"We further showed that the overexpression of USP22 increased inflammation, while knocking down BRD4 suppressed the inflammatory response in AML-12 cells."

eidos
"Accordingly , USP22 downregulation also attenuated cerebral I / R-induced oxidative stress , inflammation , and cell apoptosis in mice , thereby reducing nerve injury and neurological dysfunction [ 20 ] ."

reach
"Accordingly, USP22 downregulation also attenuated cerebral I/R-induced oxidative stress, inflammation, and cell apoptosis in mice, thereby reducing nerve injury and neurological dysfunction [20]."

reach
"The knockout of Usp22 increased inflammation associated symptoms after DSS treatment locally and systemically."
USP22 affects VIM
| 6
USP22 increases the amount of VIM.
| 3
USP22 increases the amount of VIM. 3 / 3
| 3

reach
"Molecular analysis of the tumor tissues showed that USP22 knockdown reduced the levels of cyclin D2, Akt phosphorylation, vimentin, and Bcl-2, whereas upregulated the expressions of E-cadherin, Bax, and cleaved (cl)-caspase-3, which confirmed in vitro findings."

reach
"AP4 down-regulation partially reversed the increases in N-cadherin and vimentin expression levels induced by USP22 up-regulation; however, no changes in USP22 expression levels were observed."

reach
"Western blot analysis showed that USP22 knockdown in H1650 suppressed expression of the mesenchymal markers N-cadherin and vimentin and increased expression of the epithelial markers E-cadherin and al[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 decreases the amount of VIM.
| 3
USP22 decreases the amount of VIM. 3 / 3
| 3

reach
"USP22 downregulation significantly increased the expression of E-cadherin (epithelial marker) but decreased the expression of N-cadherin and vimentin (mesenchymal markers) (XREF_FIG)."

reach
"In this study, we showed that USP22 depletion significantly decreased the expressions of BMI-1, vimentin, and snail and increased E-cadherin expression in ATC cells."

reach
"USP22 transfection significantly reversed these changes by suppressing E-cadherin and promoting vimentin expression."
USP22 affects USP51
| 4 2
USP22 inhibits USP51.
| 2
USP22 inhibits USP51. 2 / 2
| 2

reach
"To determine whether USP22 blocks association of USP27X and USP51 with SAGA, we isolated GCN5 associated proteins after shRNA mediated depletion of USP22."

reach
"To determine whether USP22 blocks association of USP27X and USP51 with SAGA, we isolated GCN5 associated proteins after shRNA mediated depletion of USP22 (XREF_FIG, lanes 2 and 3 and 5 and 6)."
USP22 binds USP51.
| 2
| 2

sparser
"To test this idea, we expressed wild type (WT) or mutant forms of USP22, USP27X and USP51 in which a conserved cysteine required for activity in USP22 is changed to serine in 293T cells ( xref )."

sparser
"To test this idea, we expressed wild-type (WT) or mutant forms of USP22, USP27X, and USP51 in which a conserved cysteine required for activity in USP22 is changed to serine in 293T cells ( Figures 3 A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 activates USP51.
| 2
USP22 activates USP51. 2 / 2
| 2

reach
"Equal numbers of cells expressing shRNAs that specifically target USP27X or USP51, but not USP22 (XREF_FIG), or expressing control shRNA, were seeded and monitored for proliferation by cell counts 72 hours later."

reach
"Equal numbers of cells expressing shRNAs that specifically target USP27X or USP51, but not USP22, or expressing control shRNA, were seeded and monitored for proliferation by cell counts 72 hr later."
USP22 affects FBP1
1 | 5
USP22 activates FBP1.
| 3
USP22 activates FBP1. 3 / 3
| 3

reach
"Moreover, it has been shown that USP22 promotes cell growth by regulating the far upstream element (FUSE)-binding protein 1 (FBP1), a transcriptional regulator of p21 [XREF_BIBR]."

reach
"Hence USP22 silencing reduces the capacity of FBP1 to repress p21 (independently of TP53 status), which in turn inhibits CDKs to prevent the G1/S transition and resulting in G1 accumulation [XREF_BIBR]."

reach
"Our results showed that USP22 silencing downregulated COX-2 and FBP1 in A549 and NCI-H460 cells compared to control siRNA."
USP22 ubiquitinates FBP1.
| 2
USP22 leads to the ubiquitination of FBP1. 2 / 2
| 2

reach
"USP22 also suppresses CDKN1A and p21 -locus expression by deubiquitinating its transcriptional repressor FBP1 (Atanassov and Dent, 2011), and acts as a negative regulator of the tumor suppressor p53 b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Recent studies have demonstrated that USP22 can inhibit the transcription of the p21 gene by de-ubiquitinating the transcriptional regulator FBP1, leading to cell proliferation and tumorigenesis [XREF_BIBR]."
USP22 deubiquitinates FBP1.
1 |
USP22 deubiquitinates FBP1. 1 / 1
1 |

reach
"Furthermore, two-sample Kolmogorov-Smirnov (KS) tests revealed statistically significant increases (siUSP22-2, siUSP22-3) and a decrease (siUSP22-Pool) in cumulative nuclear area frequency distributions relative to siControl (XREF_FIG D; Table S5) that are consistent with reduced USP22 expression inducing CIN."

reach
"In agreement with this possibility, we show that diminished USP22 expression induces CIN, highlighting a novel role for USP22 as a tumor suppressor that is essential to maintain mitotic fidelity and chromosome stability."

reach
"In this regard, while USP22 has been proposed as a novel therapeutic target based on its oncogenic functions [XREF_BIBR, XREF_BIBR, XREF_BIBR], our work suggests that USP22 inhibition will induce CIN that may promote cancer progression and/or the development of secondary malignancies."

reach
"Further, we identify USP22 as a novel CIN gene, indicating that USP22 deletions in tumors may drive CIN and contribute to oncogenesis."

reach
"Having established that reduced USP22 expression induces CIN in short-term (< 1 week) siRNA based experiments, we now sought to determine the impact long-term USP22 depletion has on CIN."

reach
"USP22 Silencing Induces CIN Associated Phenotypes."
| 1 5
USP22 activates Cell Survival.
| 1 3
| 1 3

reach
"Therefore, up-regulation of USP22 expression will lead to abnormal activation of multiple pathways to promote cell survival while down-regulation of USP22 expression can induce cell cycle arrest at G0/G1 phase in different types of cancer cells (Zhang et al., 2008)."

eidos
"Similarly , Zhao et al. reported that USP22 depletion suppressed cell survival and proliferation as well as tumor growth and lung metastasis of anaplastic thyroid carcinoma cells25 ."

reach
"USP22 was highly expressed in NPC cells and promoted cell viability and proliferation."

reach
"Silencing of either USP22 or RNF40 reduced short-term cell viability and clonogenic growth of osteosarcoma cells (Fig. 6A and B)."
USP22 inhibits Cell Survival.
| 2

reach
"Similarly, Zhao et al. reported that USP22 depletion suppressed cell survival and proliferation as well as tumor growth and lung metastasis of anaplastic thyroid carcinoma cells XREF_BIBR."

reach
"Cell viability assessed with the MTT assay showed that knock-down of USP22 and COX-2 significantly reduced cell viability to approximately 63% and 47%, respectively, of control cells, whereas overexpr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 affects CDH1
| 1 5
USP22 increases the amount of CDH1.
| 3
USP22 increases the amount of CDH1. 3 / 3
| 3

reach
"USP22 downregulation significantly increased the expression of E-cadherin (epithelial marker) but decreased the expression of N-cadherin and vimentin (mesenchymal markers) (XREF_FIG)."

reach
"Western blot analysis showed that USP22 knockdown in H1650 suppressed expression of the mesenchymal markers N-cadherin and vimentin and increased expression of the epithelial markers E-cadherin and al[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In this study, we showed that USP22 depletion significantly decreased the expressions of BMI-1, vimentin, and snail and increased E-cadherin expression in ATC cells."
USP22 inhibits CDH1.
| 1 1
USP22 inhibits CDH1. 2 / 2
| 1 1

reach
"Immunoblot analysis confirmed that USP22 knockout upregulated E-cadherin, p16; reduced ALDH1A3, Cyclin E1, c-Myc, and attenuated activation of AKT and ERK pathways in these cells."

eidos
"USP22 downregulation significantly increased the expression of E-cadherin ( epithelial marker ) but decreased the expression of N-cadherin and vimentin ( mesenchymal markers ) ( Fig. 4 ) ."
USP22 binds CDH1.
| 1
| 1

reach
"This interaction was specific because USP22 interaction with either CDH1 or FBW7 was not detected (XREF_FIG)."
TERF1 affects USP22
| 3 3
| 3 3

reach
"USP22 could bind to TRF1 and regulate telomere length (Atanassov etal., 2009)."

sparser
"For example, USP22 binding to TRF1, a protein that regulates telomere length, induces TRF1 protein stability."

sparser
"USP22 could bind to TRF1 and regulate telomere length (Atanassov et al ., xref )."

reach
"USP22 interacts with TRF1 and is required for TRF1 stability."

reach
"For example, USP22 binding to TRF1, a protein that regulates telomere length, induces TRF1 protein stability."

sparser
"USP22 interacts with TRF1 and is required for TRF1 stability."
SOS1 affects USP22
| 6
SOS1 activates USP22. 6 / 6
| 6

reach
"Furthermore, SOS1 silencing could reverse the effects of USP22 on gastric cancer cell behavior and RAS signaling both in vitro and in vivo."

reach
"These findings suggest that SOS1/RAS and downstream ERK and PI3K/AKT pathways mediate the oncogenic role of USP22 in gastric cancer."

reach
"These results suggest that SOS1/RAS signaling mediates the oncogenic role of USP22 in gastric cancer."

reach
"Furthermore, our study indicated that SOS1 was upregulated in USP22-overexpressing gastric cancer cells and xenograft tumor tissue, accompanied by activation of the RAS/ERK and PI3K/AKT pathways, suggesting that SOS1/RAS signaling mediates the oncogenic role of USP22 in gastric cancer."

reach
"Furthermore, SOS1 upregulation in USP22-overexrpessing gastric cancer cells and xenograft tumor tissue is accompanied by activation of the RAS/ERK and RAS/PI3K/AKT pathways, which is attenuated by SOS1 silencing."

reach
"Knockdown of SOS1 reverses the oncogenic effects of USP22 in gastric cancer cells."
| 1 5
| 1 5

reach
"Therefore, APC and CDC20 E3 ligase complex promotes USP22 protein degradation, presumably allowing CCNB1 degradation for cells to exit M phase."

reach
"USP22 is degraded by the APC/C E3 ubiquitin ligase complex, which also targets CCNB1 for destruction [XREF_BIBR, XREF_BIBR], thereby allowing cells to exit from mitosis, presumably by facilitating CCNB1 degradation."

reach
"In contrast, the APC and CDC20 E3 ligase complex negatively regulates USP22 activity by targeting it for degradation, presumably allowing CCNB1 downregulation so that cells can exit mitosis and enter anaphase."

reach
"To identify the E3 ligase that degrades USP22, we tested the interaction between USP22 and FBW7, CDC20, and CDH1, all of which are active during exit from mitosis [XREF_BIBR, XREF_BIBR]."

eidos
"Moreover , anaphase-promoting complex cell division cycle protein 20 ( APCCDC20 ) , an E3 ubiquitin ligase , promotes USP22 degradation in a cell cycle-dependent manner ( 61 ) ."

reach
"Our study demonstrates that USP22 is also a substrate of the APC/C E3 ligase complex, which degrades USP22 during cell exit from M phase."
MiR-4490 affects USP22
| 5
MiR-4490 activates USP22.
| 3
MiR-4490 activates USP22. 3 / 3
| 3

reach
"These findings indicate that miR-4490 targets a complementary sequence in the USP22 3 '-UTR."

reach
"Together, these results indicate that miR-4490 may inhibit GC metastasis and EMT by targeting USP22."

reach
"Although werecently developed an algorithm to predict targeting of USP22 by miR-4490, it remains to be established whether this miRNA participates in the regulation of USP22 expression in GC."
MiR-4490 decreases the amount of USP22.
| 2
MiR-4490 decreases the amount of USP22. 2 / 2
| 2

reach
"Moreover, we found that miR-4490 overexpression inhibited the expression of USP22 in GC cells, and that exogenous overexpression of USP22 partially counteracted the effects of miR-4490 on the suppression ofGC cell proliferation, migration and invasion."

reach
"We found that exogenous overexpression of miR-4490 significantly suppressed USP22 expression in GC cells, and that miR-4490 silencing increased its expression in GC cells, indicating that miR-4490 regulates USP22 expression at the posttranscriptional level."

reach
"Transcriptionally, USP22 leads to H2BK120Ub on chromatins among the FOXP3 locus to enhance its transcription."

sparser
"At the biochemical level, these Polycomb proteins function as global transcriptional repressors by catalyzing the ubiquitylation of histone H2A. In yeast, the USP22 homolog functions as a transcriptional coactivator by removing ubiquitin from a distinct core histones, H2B. Given that USP22 is expressed in cancer as part of an 11 gene signature that includes transcriptional repressors which ubiquitylate H2A, it seemed possible that USP22 might activate transcription in part via the deubiquitylation of this same substrate."

reach
"USP22 positively regulated transcription factor FOXP3 activity in mouse regulatory T (T reg) cells."

reach
"In addition, USP22 binds to the promoter region of AP4 to activate its transcription."

reach
"USP22 positively regulated transcription factor FOXP3 activity in mouse regulatory T (T reg) cells."
| 5

reach
"These findings are consistent with the idea that USP22 promotes the non T cell inflamed TME and suppresses antitumor immunity in PDA."

reach
"100 Another DUB, USP22, also stabilizes PD-L1 in tumor cells via deubiquitination and suppresses antitumor immunity in mouse tumor models."

reach
"Collectively, these experiments suggest that USP22 expression in PDA tumors cells suppresses antitumor immunity and confers resistance to immunotherapy."

reach
"Tumor cell-intrinsic USP22 suppresses antitumor immunity in pancreatic cancer."

reach
"What more excited is that USP22 can inhibit the antitumor immunity, efficacy of PDL1 targeted immunotherapy by inhibiting the deubiquitinase of PDL1 (CD274) [XREF_BIBR], which is consistent with our results."
USP22 affects YAP1
| 4 1
USP22 activates YAP1.
| 3
USP22 activates YAP1. 3 / 3
| 3

reach
"Western blot analysis of control and USP22-silenced GC cells showed that USP22 modulates the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways."

reach
"USP22 promotes GC progression by modulating FOXO1 or YAP signaling pathways via c-Myc/NAMPT/SIRT1."

reach
"Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling."
USP22 binds YAP1.
| 1 1
| 1 1

sparser
"Using IP assays, USP22 interaction with YAP at the endogenous level in A375 melanoma cells was observed ( xref )."

reach
"The interaction between USP22 and KDM3A and between KDM3A and YAP1 was further validated."
USP22 affects XPC
| 3 2
USP22 activates XPC.
| 3
USP22 activates XPC. 3 / 3
| 3

eidos
"After treatment with irradiation , XPC foci were significantly increased in LN-USP22hi and C42-USP22hi cells as well as decreased in LN-shUSP22 and C42-shUSP22 compared to corresponding controls ( Figure 5G ) , suggesting that USP22 modulates XPC activity basally and in response to genotoxic insult ."

eidos
"Moreover , as Rad23B partners with XPC to sense and initiate NER , Rad23B foci formation was also increased basally and after irradiation in LN-USP22hi and C42-USP22hi cells ( Supplemental Figure 5F ) , further suggesting USP22 upregulation augments XPC activity ."

eidos
"USP22 induced deubiquitylation of XPC without an increase of the protein half-life ( Supplemental Figure 5A ) , suggesting the alternative hypothesis that USP22 may modulate XPC activity through de-polyubiquitylation , as XPC is known to be polyubiquitylated to promote efficient DNA repair [ 32,33,39 ] ."
USP22 binds XPC.
| 2
| 2

sparser
"This interaction occurred in control cells as well, indicating that XPC and USP22 interact regardless of USP22 overexpression ( xref )."

sparser
"An interaction between USP22 and XPC also occurred in the GEMM-derived MAFs, GFP and hUSP22 cells ( xref )."
USP22 affects USP27X
| 4 1
USP22 inhibits USP27X.
| 2
USP22 inhibits USP27X. 2 / 2
| 2

reach
"To determine whether USP22 blocks association of USP27X and USP51 with SAGA, we isolated GCN5 associated proteins after shRNA mediated depletion of USP22 (XREF_FIG, lanes 2 and 3 and 5 and 6)."

reach
"To determine whether USP22 blocks association of USP27X and USP51 with SAGA, we isolated GCN5 associated proteins after shRNA mediated depletion of USP22."
USP22 activates USP27X.
| 2
USP22 activates USP27X. 2 / 2
| 2

reach
"Equal numbers of cells expressing shRNAs that specifically target USP27X or USP51, but not USP22, or expressing control shRNA, were seeded and monitored for proliferation by cell counts 72 hr later."

reach
"Equal numbers of cells expressing shRNAs that specifically target USP27X or USP51, but not USP22 (XREF_FIG), or expressing control shRNA, were seeded and monitored for proliferation by cell counts 72 hours later."
USP22 binds USP27X.
| 1
USP22 binds USP27X. 1 / 1
| 1

sparser
"All these results indicate that USP27X and the close homologue USP22 specifically interact and stabilize Snail1."
USP22 affects SOS1
| 5
USP22 activates SOS1.
| 3
USP22 activates SOS1. 3 / 3
| 3

reach
"In this study, using a ChIP assay, we demonstrated, for the first time, that the overexpression of USP22 induced the upregulation of RAS activator SOS1 in SGC7901 cells."

reach
"USP22 overexpression in gastric cancer cells induces the upregulation of SOS1 and activation of the RAS/ERK and PI3K/AKT pathways."

reach
"Chromatin immunoprecipitation revealed that the overexpression of USP22 induced the upregulation of RAS activator son of sevenless 1 (SOS1) in SGC7901 cells."
USP22 increases the amount of SOS1.
| 2
USP22 increases the amount of SOS1. 2 / 2
| 2

reach
"Indeed, USP22 overexpression induces significant elevations in protein levels of SOS1, RAS, p-ERK, p-PI3K, and p-AKT in both SGC7901 cells and tumors."

reach
"The results showed that overexpression of USP22 induced considerable upregulation of SOS1 expression in SGC7901 cells, accompanied by significant upregulation of RAS, p-ERK, c-myc, p-PI3K, and p-AKT (Fig. 5b, left panel)."
USP22 affects NSCLC
| 5
USP22 activates NSCLC. 5 / 5
| 5

reach
"Therefore, our results from the mouse xenograft model demonstrate that USP22 silencing inhibits NSCLC tumorigenesis in vivo through regulating the MDMX-p53 pathway."

reach
"USP22 promotes NSCLC tumorigenesis via MDMX up-regulation and subsequent p53 inhibition."

reach
"Taken together, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition."

reach
"In summary, our results suggest that USP22 promotes NSCLC tumorigenesis in vitro and in vivo through MDMX upregulation and subsequent p53 inhibition."

reach
"However, whether USP22 promotes tumorigenesis in NSCLC remains unclear."
USP22 affects NFATC2
2 1 | 2
USP22 binds NFATC2.
2 | 1
2 | 1

No evidence text available

No evidence text available

reach
"Gao et al found that USP22 interacts with and deubiquitinates NFATc2, and also stabilizes NFATc2 protein and promotes NFATc2 function to facilitate IL-2 expression in T cells."
USP22 deubiquitinates NFATC2.
1 | 1
USP22 deubiquitinates NFATC2. 2 / 2
1 | 1

reach
"Gao et al found that USP22 interacts with and deubiquitinates NFATc2, and also stabilizes NFATc2 protein and promotes NFATc2 function to facilitate IL-2 expression in T cells."
USP22 affects LINC01426
| 5
USP22 binds LINC01426. 5 / 5
| 5

reach
"Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22."

reach
"LINC01426 binds with USP22 to promote SHH deubiquitination."

reach
"Pull-down Silver staining followed by western blot analysis further demonstrated the interaction between LINC01426 and USP22 in PC-9 and Calu3 cells."

reach
"Here, we determined that LINC01426 interacted with USP22 to stabilize SHH protein."

reach
"Here, we uncovered that LINC01426 could interact with USP22 in LUAD cells."
USP22 affects KPNA2
| 1 1 3
USP22 binds KPNA2.
| 3
| 3

sparser
"Results from endogenous immunoprecipitation assays suggest that KPNA2 interacted with USP22 constitutively but interacted with IRF3 or pIRF3 in THP-1 cells in a manner dependent on viral infection ( xref )."

sparser
"In contrast, mutation of USP22 NLS (USP22-RR/AA) did not affect its association with KPNA2 ( xref ), suggesting that USP22 interacts with KPNA2 independently of its NLS."

sparser
"In our study, we found that knockout of USP22 impaired virus-triggered nuclear translocation of p65 and induction of p65-target genes such as Tnf and Il6 , which was restored by reconstitution of KPNA2, suggesting a role of the USP22KPNA2 axis in NF-κB activation after viral infection (data not shown)."
USP22 deubiquitinates KPNA2.
| 1 1
USP22 leads to the deubiquitination of KPNA2. 2 / 2
| 1 1

trips
"USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2."

reach
"USP22 promotes IRF3 nuclear translocation and antiviral responses by deubiquitinating the importin protein KPNA2."
USP22 affects H2AX
| 4 1
USP22 leads to the phosphorylation of H2AX. 5 / 5
| 4 1

reach
"Our findings in lung adenocarcinoma cell line and xenografts support that USP22 could promote the phosphorylation of histone H2AX via deubiquitinating histone H2A, thus contributing to the DNA damage repair induced by cisplatin and leading to cisplatin resistance."

sparser
"Our findings in lung adenocarcinoma cell line (Figure xref ) and xenografts (Figure xref ) support that USP22 could promote the phosphorylation of histone H2AX via deubiquitinating histone H2A, thus contributing to the DNA damage repair induced by cisplatin and leading to cisplatin resistance."

reach
"The results confirm that USP22 could deubiquitinate H2A and promote the phosphorylation of histone H2AX, thus contributing to DNA damage repair and inducing cisplatin resistance in A549 cells."

reach
"USP22 enhances DNA damage repair and induce cisplatin resistance by promoting the phosphorylation of histone H2AX via deubiquitinating histone H2A."

reach
"USP22 Enhances DNA Damage Repair and Induces Cisplatin Resistance by Promoting the Phosphorylation of Histone H2AX via Deubiquitinating Histone H2A."
USP22 affects FOXM1
| 4
USP22 increases the amount of FOXM1. 4 / 5
| 4

reach
"Mechanistically, it has been reported that USP22 induces β-catenin nuclear localisation and upregulates FoxM1 expression to promote G1/S cell cycle transition and cell proliferation (Ning et al., 2014)."

reach
"USP22 promotes the G1/S phase transition by upregulating FoxM1 expression via promoting beta-catenin nuclear localization."

reach
"USP22 promotes the G1/S phase transition by upregulating FoxM1 expression via beta-catenin nuclear localization and is associated with poor prognosis in stage II pancreatic ductal adenocarcinoma."

reach
"Similarly, in pancreatic ductal adenocarcinoma cells, USP22 promotes the G1/S transition and proliferation by upregulating the expression of FoxM1 [8], a key regulator of the G1/S and G2/M cell cycle transitions [32]."
USP22 affects ERK
| 5
USP22 activates ERK.
| 4
USP22 activates ERK. 4 / 4
| 4

reach
"Activation of ERK1/2 kinase rather than AKT1 by USP22 was found to be one of the mechanisms promoting LC3 processing."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS and ERK and PI3K and AKT pathways in SGC7901 cells and xenograft tumor tissues."

reach
"USP22 overexpression in gastric cancer cells induces the upregulation of SOS1 and activation of the RAS/ERK and PI3K/AKT pathways."

reach
"Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues."
USP22 increases the amount of ERK.
| 1
USP22 increases the amount of phosphorylated ERK. 1 / 1
| 1

reach
"Indeed, USP22 overexpression induces significant elevations in protein levels of SOS1, RAS, p-ERK, p-PI3K, and p-AKT in both SGC7901 cells and tumors."
USP22 affects BRCA2
| 5
USP22 increases the amount of BRCA2. 5 / 5
| 5

reach
"Lastly, we show USP22 positively regulates BRCA2 and PALB2 levels at the protein level."

reach
"USP22 modulates PALB2 and BRCA2 levels to promote chemoresistance in lung adenocarcinoma."

reach
"To determine whether USP22 is modulating PALB2 and BRCA2 protein levels at the transcriptional level we performed qPCR of BRCA2 and PALB2 with and without USP22 knockdown after 48 hours (Figure S1b)."

reach
"To further validate USP22 was modulating and stabilizing BRCA2 and PALB2 levels at the translational level, cells were depleted of USP22 again with and without treatment of the proteasome inhibitor MG132 to see if this could rescue PALB2 and BRCA2 levels in a USP22 knockdown background (Figure S1c)."

reach
"Our study reveals USP22 positively regulates PALB2 and BRCA2 levels at the translational level."
TP53 affects USP22
| 5
TP53 decreases the amount of USP22.
| 3
TP53 decreases the amount of USP22. 3 / 3
| 3

reach
"In p53 wild-type colorectal cancer (CRC) cells, hydrogen peroxide (H 2 O 2 )-induced p53 expression represses the transcription of deubiquitinase USP22, which otherwise deubiquitinates and stabilizes Fatty Acid Synthase (FASN), and thus inhibits fatty acid synthesis."

reach
"P53 transcriptionally represses USP22 expression under H 2 O 2 treatment."

reach
"We have found H O -induced p53 expression inhibits the transcription of USP22, which otherwise deubiquitinates and stabilizes FASN."
TP53 inhibits USP22.
| 2
TP53 inhibits USP22. 2 / 2
| 2

reach
"Our study demonstrates that p53 represses USP22-mediated stabilization of FASN, thus provides an alternative pathway connecting p53 and fatty acid synthesis."

reach
"To further validate the effect of p53 on USP22 expression, we depleted p53 in RKO and HCT116 cells, and found USP22 was increased by p53 depletion at both protein and mRNA levels (Fig. 4C, D)."
PTEN affects USP22
| 2 3
PTEN binds USP22.
| 1 3
| 1 3

sparser
"USP22 bound to PTEN and stabilized PTEN expression by decreasing its ubiquitination."

sparser
"Subsequently, the PTENUSP22 interaction was confirmed by endogenous immunoprecipitation analysis in both SW1990 and HPAC cells (Fig.  xref )."

reach
"USP22 bound to PTEN and stabilized PTEN expression by decreasing its ubiquitination."

sparser
"We found that PTEN might interact with USP22 (Fig.  xref , and xref )."
PTEN activates USP22.
| 1
PTEN activates USP22. 1 / 1
| 1

reach
"PTEN overexpression reversed the promoting effect of USP22 knockdown on cell viability and the inhibitory effects of USP22 knockdown on apoptosis, oxidative stress, and LDH release rate in PC12 cells subjected to OGD/R."
Neoplasms affects USP22
| 3
Neoplasms increases the amount of USP22.
| 1
Neoplasms increases the amount of USP22. 1 / 3
| 1

reach
"Supporting that, a more quantitative me-RIP-qPCR analysis on tumor tissues from ALKBH5 KD group and ALKBH5-silenced osteosarcoma cells showed significantly increased m A levels and decreased expression of USP22 compared with scrambled group (Supplementary Fig. S8B and S8C)."
Neoplasms activates USP22.
| 2
| 2

reach
"IHC staining showed that the tumors developed from USP22-overexpressing SGC7901 cells had significantly increased USP22 and Ki-67 staining and decreased TUNEL staining, compared with the control group (Fig. 4d)."

reach
"Furthermore, our study indicated that SOS1 was upregulated in USP22-overexpressing gastric cancer cells and xenograft tumor tissue, accompanied by activation of the RAS/ERK and PI3K/AKT pathways, suggesting that SOS1/RAS signaling mediates the oncogenic role of USP22 in gastric cancer."
LINC01426 affects USP22
| 5
USP22 binds LINC01426. 5 / 5
| 5

reach
"Pull-down sliver staining and RIP assay revealed that LINC01426 could interact with USP22."

reach
"LINC01426 binds with USP22 to promote SHH deubiquitination."

reach
"Pull-down Silver staining followed by western blot analysis further demonstrated the interaction between LINC01426 and USP22 in PC-9 and Calu3 cells."

reach
"Here, we determined that LINC01426 interacted with USP22 to stabilize SHH protein."

reach
"Here, we uncovered that LINC01426 could interact with USP22 in LUAD cells."
Gal-SLPs affects USP22
| 4 1
Gal-SLPs inhibits USP22.
| 4
Gal-SLPs inhibits USP22. 4 / 4
| 4

eidos
"Besides , Gal-SLPs downregulated in vivo USP22 expression to a much greater extent than Gal-LPs ( Figure 7g ) , which was well correlated with the in vitro Western blot analysis , convincingly proving the self-activated cascade-responsive process and synergy of sorafenib and shUSP22 ."

eidos
"] Our study provided strong evidence that the downregulation of USP22 by Gal-SLPs suppressed the expression of MRP1 and caused high intracellular sorafenib accumulation ."

eidos
"Thus , Gal-SLPs dramatically suppressed the expression of USP22 ."

eidos
"Thus , we speculated that the downregulation of USP22 by Gal-SLPs could block the glycolysis and further suppress stemness features in HCC cells ."
Gal-SLPs decreases the amount of USP22.
| 1
Gal-SLPs decreases the amount of USP22. 1 / 1
| 1

reach
"Thus, Gal-SLPs dramatically suppressed the expression of USP22."
AKT affects USP22
| 4 1
AKT inhibits USP22.
| 2 1
AKT inhibits USP22. 3 / 3
| 2 1

reach
"USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5-Fu by up-regulation of Smad4 and suppression of Akt."

sparser
"Silencing Smad4 blocked USP22 knockdown-induced Akt inhibition in Bel/Fu cells."

reach
"These results suggest that USP22 knockdown induced chemosensitivity of HCC cells by down-regualting PI3K and Akt, and Smad4 mediated Akt suppression as well."
AKT activates USP22.
| 2
AKT activates USP22. 2 / 2
| 2

reach
"Western blot analysis was conducted to detect the activation of RAS and ERK and PI3K and AKT signaling in USP22 overexpressing SGC7901 cells and xenograft tumor tissues."

reach
"These findings suggest that SOS1/RAS and downstream ERK and PI3K/AKT pathways mediate the oncogenic role of USP22 in gastric cancer."
MiR-34b affects USP22
| 4
MiR-34b decreases the amount of USP22.
| 2
MiR-34b decreases the amount of USP22. 2 / 2
| 2

reach
"Furthermore, we demonstrated that miR-34b inhibited NPC proliferation by downregulating the expression of USP22."

reach
"qRT-PCR and Western blot data show that miR-34b transfection significantly suppressed the level of USP22 (XREF_FIG)."
MiR-34b activates USP22.
| 2
MiR-34b activates USP22. 2 / 2
| 2

reach
"To investigate whether miR-34b inhibits NPC cell proliferation by targeting USP22, we transfected SUNE-6-10B cells and a cell line that was stably expressing USP22 (XREF_FIG) with miR-34b mimics."

reach
"Notably, the overexpression of USP22 rescued the inhibitory effect of miR-34b on NPC, demonstrating that miR-34b suppresses the proliferation of NPC by targeting USP22."
MiR-30e-5p affects USP22
| 4
MiR-30e-5p decreases the amount of USP22.
| 2
MiR-30e-5p decreases the amount of USP22. 2 / 2
| 2

reach
"Molecular mechanism analysis con firmed that miR-30e-5p could negatively regulate mRNA and protein levels of USP22 by binding to its specific sequence of 3 ' UTR."

reach
"Luciferase reporter assays showed that miR-30e-5p negatively regulated USP22 expression by binding to a specific sequence in the 3 ' UTR."
MiR-30e-5p activates USP22.
| 2
MiR-30e-5p activates USP22. 2 / 2
| 2

reach
"In this study, we investigated whether miR-30e-5p inhibits tumor growth by targeting USP22 in NSCLC."

reach
"MiR-30e-5p inhibits the proliferation and metastasis of nasopharyngeal carcinoma cells by targeting USP22."
USP22 affects miR-132-3p
| 4
USP22 activates miR-132-3p. 4 / 4
| 4

reach
"USP22 Was a Target of miR-132-3p in CRC."

reach
"Besides, USP22 was a target of miR-132-3p, and its overexpression restored the inhibition effect of miR-132-3p mimic on CRC cell progression."

reach
"In terms of mechanism, our results revealed that USP22 was a target of miR-132-3p."

reach
"Overexpressed USP22 Restored the Inhibition Effects of miR-132-3p on CRC Cell Progression."
| 2 2

reach
"USP22 promotes hypoxia induced HCC stemness and glycolysis by deubiquitinating and stabilising HIF1alpha."

reach
"USP22 contributes to chemoresistance, stemness, and EMT phenotype of TNBC cells by suppressing the glycolysis via c-Myc deubiquitination."

eidos
"In particular , Gal-SLPs can induce a trio synergetic effect : i ) sorafenib elevated intracellular levels of ROS , which oxidize B-PDEAEA to trigger rapid shUSP22 release for efficient gene downregulation ; ii ) the downregulation of USP22 led to downregulation of multidrug resistance-associated protein 1 ( MRP1 ) and inhibition of glycolysis , dramatically impairing MDR and achieving higher intracellular sorafenib accumulation , thus generating an ROS-responsive positive feedback loop ; iii ) the downregulation of USP22 suppressed the cell metabolism of cancer cells and further influenced cancer stemness ."

eidos
"Thus , we speculated that the downregulation of USP22 by Gal-SLPs could block the glycolysis and further suppress stemness features in HCC cells ."
USP22 affects cell
| 4
USP22 inhibits cell.
| 2
USP22 inhibits cell. 2 / 2
| 2

eidos
"USP22 is a member of the deubiquitinating enzyme ( DUB ) family , which is related to the occurrence and development of various tumor types , including CRC.26-28 Depletion of USP22 led to the accumulation in G1 phase and blocked the proliferation of CRC cells ."

eidos
"Furthermore , knockdown of USP22 modulated the expression of many genes in HeLa cells ."
USP22 activates cell.
| 2
USP22 activates cell. 2 / 2
| 2

eidos
"USP22 depletion decreased cell proliferation , migration , Vascular Mimicry ( VM ) formation , and angiogenesis ."

eidos
"The present results indicate that USP22 may regulate survivin via deubiquitination , thereby promoting the proliferation of RCC cells ."
USP22 affects cell death
| 1 2
USP22 activates cell death.
| 1 1
| 1 1

reach
"While it is clear that USP22 is overexpressed in various cancer types and may promote oncogenesis by altering gene expression, cell death and cell cycle progression, emerging evidence suggests that USP22 also harbors tumor suppressor like properties."

eidos
"In addition to USP2-1 , USP2-2 also caused caspase-8 activation , cleavage of poly ADP-ribose polymerase ( PARP ) , and promotion of cell death [ 78 ] ."
USP22 inhibits cell death.
| 1
| 1

reach
"Moreover, USP22, SIRT1, or SLC7A11 elevation contributed to enhanced cardiomyocyte viability and attenuated ferroptosis induced cell death in vitro, accompanied by increased GSH levels, as well as decreased reactive oxygen species production, lipid peroxidation, and iron accumulation."
USP22 affects Wnt/β-catenin
| 4
USP22 inhibits Wnt/β-catenin.
| 2
USP22 inhibits Wnt/β-catenin. 2 / 2
| 2

reach
"Down-regulation of USP22 reduces cell stemness and enhances the sensitivity of pancreatic cancer cells to cisplatin by inactivating the Wnt/β-catenin pathway."

reach
"Inhibition of USP22 reduced the cell stemness and augmented the sensitivity of PC cells to cisplatin by inhibiting the Wnt/β-catenin pathway."
USP22 activates Wnt/β-catenin.
| 2
USP22 activates Wnt/β-catenin. 2 / 2
| 2

reach
"Silencing USP22 can inhibit the Wnt/β-catenin pathway to reduce cell stemness and enhance the sensitivity of PC cells to cisplatin."

reach
"Silencing USP22 inhibited the Wnt/β-catenin pathway."
USP22 affects TRRAP
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP22 affects STAT1
| 3 1
USP22 inhibits STAT1.
| 3
USP22 inhibits STAT1. 3 / 3
| 3

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"USP22-deficient hIECs strongly 46 upregulate genes involved in IFN signaling and viral defense, including numerous IFN-47 stimulated genes (ISGs), with increased secretion of IFN-λ and enhanced STAT1 48 signaling, even in the absence of exogenous IFNs or viral infection."
| DOI

reach
"USP22-deficient hIECs strongly upregulate genes involved in IFN signaling and viral defense, including numerous IFN-stimulated genes (ISGs), with increased secretion of IFN-λ and enhanced STAT1 signaling, even in the absence of exogenous IFNs or viral infection."

reach
"211 212 USP22 negatively regulates STAT1 signaling and IFN-λ1 expression 213 The expression of ISGs is typically induced upon activation of IFN signaling pathways 214 during pathogen invasion or autoinflammatory disease and serves to control 215 inflammation and other defensive mechanisms 9 ."
| DOI
USP22 phosphorylates STAT1.
| 1
USP22 phosphorylates STAT1. 1 / 1
| 1

sparser
"Interestingly, despite efficient KO of the 245 individual PRRs in both NHT and USP22 KO HT-29 cells, additional deletion of RIG-I, 246 MDA5 or TLR3 did not decrease USP22-dependent STAT1 phosphorylation or ISG56 247 expression (Figure 4B -D)."
| DOI
USP22 affects SP1
| 4
| 4

sparser
"Results showed that Sp1 binds to the USP22 promoter in fibroblasts, suggesting that Sp1-DNA interaction may be required for USP22 repression."

sparser
"For example, SP1 and protein kinase A/cAMP response element-binding protein could bind to the USP22 promoter to suppress or promote USP22 transcription, respectively ( xref , xref )."

sparser
"Immunoprecipitation of cross-linked chromatin from HFL1 cells with an anti-Sp1 antibody followed by PCR amplification of the region (the sequence between-210 and +52) confirmed that the endogenous Sp1 protein does bind to this region of the USP22 promoter in HFL1 ( xref )."

sparser
"Interaction between Sp1 and the USP22 Promoter."
USP22 affects SCARA3
| 4
USP22 inhibits SCARA3.
| 2
USP22 inhibits SCARA3. 2 / 2
| 2

reach
"Using these AID -/- CH12 cells, we found that Eny2-, Atxn7-, and Usp22 knockdown led to a ~ 30% reduction in CRISPR and Cas9 mediated CSR compared to controls."

reach
"Using these AID -/- CH12 cells, we found that Eny2-, Atxn7-, and Usp22 knockdown led to a ~ 30% reduction in CRISPR and Cas9 mediated CSR compared to controls (XREF_FIG and XREF_SUPPLEMENTARY)."
USP22 activates SCARA3.
| 2
USP22 activates SCARA3. 2 / 2
| 2

reach
"Surprisingly, Usp22 depletion causes defects in CSR to various Ig isotypes, but not IgA."

reach
"We demonstrate that Usp22 promotes c-NHEJ and CSR in vivo."
USP22 affects PTEN
| 1 3
| 1 3

sparser
"USP22 bound to PTEN and stabilized PTEN expression by decreasing its ubiquitination."

sparser
"Subsequently, the PTENUSP22 interaction was confirmed by endogenous immunoprecipitation analysis in both SW1990 and HPAC cells (Fig.  xref )."

reach
"USP22 bound to PTEN and stabilized PTEN expression by decreasing its ubiquitination."

sparser
"We found that PTEN might interact with USP22 (Fig.  xref , and xref )."
USP22 affects NLRP3
| 1 3
USP22 inhibits NLRP3.
| 1 2
USP22 inhibits NLRP3. 3 / 3
| 1 2

eidos
"Here , we demonstrated that USP22 ( ubiquitin specific peptidase 22 ) promotes NLRP3 degradation and inhibits NLRP3 inflammasome activation ."

reach
"Here, we demonstrated that USP22 (ubiquitin specific peptidase 22) promotes NLRP3 degradation and inhibits NLRP3 inflammasome activation."

reach
"USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy."
USP22 activates NLRP3.
| 1
USP22 activates NLRP3. 1 / 1
| 1

reach
"USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy."
USP22 affects MMP9
| 4
USP22 activates MMP9. 4 / 4
| 4

reach
"USP22 and STAT3 co-depletion partly rescued the MMP9 proteolytic activity and invasion of SW480 cells, compared with that of STAT3 depletion alone."

reach
"In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3 and MMP9 signaling pathway."

reach
"Other inflammatory mediators secreted by PDA cells include granulocyte colony-stimulating factor (G-CSF) (41), IL-6 (42), IL-1α (43), IL-1β (44, 45), ubiquitin specific peptidase 22 (USP22) (46), C-X-C motif chemokine ligand 8 (CXCL8) (47), matrix metallopeptidase 9 (MMP-9) and indoleamine-2,3-dioxygenase (IDO) (48), which all contribute to the establishment of immunosuppressive TME in pancreatic cancer ( Figure 1 )."

reach
"In colon cancer, USP22 was reported to attenuate the invasion capacity of colon cancer cells by inhibiting the STAT3 and MMP9 signaling pathway."
USP22 affects FlaG
| 4
| 4

sparser
"Consistent with our LacO array recruitment experiment, ( xref ) mCherry-PALB2 WD40 4X could not pull-down FLAG-USP22 WT while mCherry-PALB2 WD40 WT robustly bound FLAG-USP22 WT ."

sparser
"Using an mCherry tagged version of this mutant (mCherry-PALB2 WD40 4X ) we performed an IP experiment in H1299 lung adenocarcinoma cells to assess its ability to pull down FLAG-USP22 WT ( xref )."

sparser
"The fragment mCherry-PALB2 Nterm that does not contain the WD40 domain was not able to pull-down FLAG-USP22 WT validating our previous LacO array data ( xref )."

sparser
"Furthermore, overexpression of siRNA resistant FLAG-USP22 in U2OS FOKI cells rescues the localization of BRCA2, PALB2, and Rad51 to the array after DNA damage."
USP22 affects FOXP3
| 4
USP22 decreases the amount of FOXP3.
| 2
USP22 decreases the amount of FOXP3. 2 / 2
| 2

reach
"Screen hits were confirmed using individual ribonucleoprotein sgRNA-Cas9 complexes (RNPs), which showed that targeting Usp22 in both mouse and human Tregs (USP22) decreased FOXP3 expression, again suggesting a role in positively regulating FOXP3 expression."

reach
"T reg -specific ablation of Usp22 in mice reduced Foxp3 protein levels and caused defects in their suppressive function that led to spontaneous autoimmunity but protected against tumour growth in multiple cancer models."
USP22 activates FOXP3.
| 2
USP22 activates FOXP3. 2 / 2
| 2

reach
"USP22 positively regulated transcription factor FOXP3 activity in mouse regulatory T (T reg) cells."

reach
"USP22 positively regulated transcription factor FOXP3 activity in mouse regulatory T (T reg) cells."
USP22 affects FN1
| 4
USP22 increases the amount of FN1.
| 2
USP22 increases the amount of FN1. 2 / 2
| 2

reach
"Ubiquitin specific protease 22 (USP22) reduces the degradation of sirtuin-1 and the expression of FN and TGF-beta1 in AGE treated GMCs, whereas depletion of USP22 promotes sirtuin-1 degradation and the expression of FN and TGF-beta1 in this cell model."

reach
"Ubiquitin specific protease 22 (USP22) reduced Sirt1 ubiquitination and degradation and decreased FN and TGF-beta1 expression in GMCs under both basal and AGEs treated conditions."
USP22 decreases the amount of FN1.
| 2
USP22 decreases the amount of FN1. 2 / 2
| 2

reach
"Ubiquitin specific protease 22 (USP22) reduced Sirt1 ubiquitination and degradation and decreased FN and TGF-beta1 expression in GMCs under both basal and AGEs treated conditions."

reach
"Ubiquitin specific protease 22 (USP22) reduces the degradation of sirtuin-1 and the expression of FN and TGF-beta1 in AGE treated GMCs, whereas depletion of USP22 promotes sirtuin-1 degradation and the expression of FN and TGF-beta1 in this cell model."
USP22 affects BCL2
| 4
USP22 increases the amount of BCL2. 4 / 4
| 4

reach
"Molecular analysis of the tumor tissues showed that USP22 knockdown reduced the levels of cyclin D2, Akt phosphorylation, vimentin, and Bcl-2, whereas upregulated the expressions of E-cadherin, Bax, and cleaved (cl)-caspase-3, which confirmed in vitro findings."

reach
"This may explain changes in BAD and bcl-2 expression in response to USP22 overexpression.To investigate whether SOS1 plays an essential role in mediating the tumorigenic roles of USP22 in gastric cancer, we silenced its expression in USP22-overexpressing SGC7901 cells."

reach
"USP22 knockdown also decreased the expression of Bcl-XL and Bcl-2 and increased the expression of cleaved-caspase 3 and cleaved-caspase 9."

reach
"We also noticed that overexpression of USP22 induced significant alterations in apoptosis-related BAD and bcl-2 expression."
USP22 affects AP4
| 4
USP22 binds AP4. 4 / 4
| 4

sparser
"We also found that USP22 binds to the promoter region of AP4 to mediate its transcription and thus induce CRC cell EMT."

sparser
"In addition, USP22 binds to the promoter region of AP4 to activate its transcription."

sparser
"Additionally, assessment of CRC clinicopathological characteristics demonstrated that USP22 and AP4 expression levels were significantly associated with pT classification, pM classification, AJCC stage and tumor markers used as prognostic indicators of postoperative recurrence and metastasis in CRC, including CEA and CA199."

sparser
"Consistent with the above results, ChIP analysis revealed that USP22 binds the promoter region of AP4 (Figure xref )."
USP22 affects AASDHPPT
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
TRRAP affects USP22
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
HDAC1 affects USP22
| 1 2 1
HDAC1 inhibits USP22.
| 1 1 1
HDAC1 inhibits USP22. 3 / 3
| 1 1 1

eidos
"The most potent inhibitor , hD1 , inhibits USP22 in vitro with a Ki of 180 nM ( Figure 3A ) ."

sparser
"As shown in xref , linear hD1 inhibits USP22 at a ~4-fold higher concentration, indicating the constraining the peptide does not play a major role in the effectiveness of this inhibitor."

reach
"As shown in figure 3B, linear hD1 inhibits USP22 at a ~4-fold higher concentration, indicating the constraining the peptide does not play a major role in the effectiveness of this inhibitor."
HDAC1 activates USP22.
| 1
HDAC1 activates USP22. 1 / 1
| 1

reach
"The most potent inhibitor, hD1, inhibits USP22 in vitro with a K of 180 nM (Figure 3A)."
FlaG affects USP22
| 4
| 4

sparser
"Consistent with our LacO array recruitment experiment, ( xref ) mCherry-PALB2 WD40 4X could not pull-down FLAG-USP22 WT while mCherry-PALB2 WD40 WT robustly bound FLAG-USP22 WT ."

sparser
"Using an mCherry tagged version of this mutant (mCherry-PALB2 WD40 4X ) we performed an IP experiment in H1299 lung adenocarcinoma cells to assess its ability to pull down FLAG-USP22 WT ( xref )."

sparser
"The fragment mCherry-PALB2 Nterm that does not contain the WD40 domain was not able to pull-down FLAG-USP22 WT validating our previous LacO array data ( xref )."

sparser
"Furthermore, overexpression of siRNA resistant FLAG-USP22 in U2OS FOKI cells rescues the localization of BRCA2, PALB2, and Rad51 to the array after DNA damage."
APC_C affects USP22
| 4
APC_C ubiquitinates USP22.
| 2
APC_C ubiquitinates USP22. 2 / 2
| 2

reach
"Lastly, ubiquitylation of USP22 mediated by the anaphase promoter complex and cyclosome (APC/C) induces USP22 protein degradation during the cell cycle [XREF_BIBR]."

reach
"Fourth, USP22 is ubiquitinated and degraded by CDC20 containing APC/C complex during cell exit from M phase, presumably to release the brake on CCNB1 degradation."
APC_C inhibits USP22.
| 2
APC_C inhibits USP22. 2 / 2
| 2

reach
"Our study demonstrates that USP22 is also a substrate of the APC/C E3 ligase complex, which degrades USP22 during cell exit from M phase."

reach
"USP22 is degraded by the APC/C E3 ubiquitin ligase complex, which also targets CCNB1 for destruction [XREF_BIBR, XREF_BIBR], thereby allowing cells to exit from mitosis, presumably by facilitating CCNB1 degradation."
AP4 affects USP22
| 4
USP22 binds AP4. 4 / 4
| 4

sparser
"We also found that USP22 binds to the promoter region of AP4 to mediate its transcription and thus induce CRC cell EMT."

sparser
"In addition, USP22 binds to the promoter region of AP4 to activate its transcription."

sparser
"Additionally, assessment of CRC clinicopathological characteristics demonstrated that USP22 and AP4 expression levels were significantly associated with pT classification, pM classification, AJCC stage and tumor markers used as prognostic indicators of postoperative recurrence and metastasis in CRC, including CEA and CA199."

sparser
"Consistent with the above results, ChIP analysis revealed that USP22 binds the promoter region of AP4 (Figure xref )."
AASDHPPT affects USP22
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
3 |
Valproic acid decreases the amount of USP22.
2 |
Valproic acid decreases the amount of USP22. 2 / 2
2 |

No evidence text available

No evidence text available
Valproic acid methylates USP22.
1 |
1 |

No evidence text available
MiR-30-5p affects USP22
| 3
MiR-30-5p inhibits USP22.
| 1
MiR-30-5p inhibits USP22. 1 / 1
| 1

reach
"Jiang et al. (2019) have demonstrated that overexpression of miR-30-5p negatively regulates the expression of Wnt/β-catenin pathway target genes (Axin2 and c-Myc) and inhibits chemoresistance in CRC cells by targeting ubiquitin-specific peptidase 22 (USP22)."
MiR-30-5p decreases the amount of USP22.
| 1
MiR-30-5p decreases the amount of USP22. 1 / 1
| 1

reach
"Western blot assays showed that miR-30-5p decreased USP22 protein expression in HEK293 and Caco2 CRC cells."
MiR-30-5p binds USP22.
| 1
USP22 binds miR-30-5p. 1 / 1
| 1

reach
"Furthermore, the binding of USP22 with the miR-30-5p family was confirmed by luciferase assay."
XPC affects USP22
| 1 2
XPC binds USP22.
| 2
| 2

sparser
"This interaction occurred in control cells as well, indicating that XPC and USP22 interact regardless of USP22 overexpression ( xref )."

sparser
"An interaction between USP22 and XPC also occurred in the GEMM-derived MAFs, GFP and hUSP22 cells ( xref )."
XPC activates USP22.
| 1
XPC activates USP22. 1 / 1
| 1

reach
"Thus, XPC undergoes deubiquitylation as a result of USP22 function and promotes USP22 mediated survival to DNA damage."

reach
"Moreover, USP22 promotes both HR (23) and NHEJ (48, 59)."

reach
"USP22 Is Necessary for Efficient HR."

reach
"In this study we show that USP22 is necessary for HR, localizes at sites of DNA damage, and is necessary for recruitment of the PALB2-BRCA2-Rad51 complex through stabilizing PALB2 and BRCA2 protein levels at the translational level."
USP22 affects cellular survival
| 3
USP22 activates cellular survival. 3 / 3
| 3

eidos
"Accordingly , USP22 promotes cellular survival after double strand break-inducing irradiation ( Figure 2 ; Supplemental Figure 2 ; Figure 3 ) ."

eidos
"The USP22-sensitive ubiquitylome reveals altered modification of DNA repair-related proteins The USP22-sensitive transcriptome implicated USP22 in affecting DDR-related pathways ( Figure 2 ) , and in vitro and in vivo studies demonstrated that USP22 modulates proliferative phenotypes as well as cellular survival ( Figures 2-3 ) ."

eidos
"Moreover , USP22 depletion decreased cellular survival in response to cisplatin at 2.5 muM ( 1.9-fold ; p =0 .004 ) and 5 muM ( 3.5-fold ; p =0 .0002 ) in CRPC cells ( Figure 2E , right ) as well as HT-sensitive cells ( p =0 .001 ; Supplemental Figure 2E , right ) , indicating that USP22 is required for cellular survival after DNA damage ."
USP22 affects cell stemness
| 3
USP22 activates cell stemness. 3 / 3
| 3

eidos
"Down-regulation of USP22 reduces cell stemness and enhances the sensitivity of pancreatic cancer cells to cisplatin by inactivating the Wnt / beta-catenin pathway ."

eidos
"Inhibition of USP22 reduced the cell stemness and augmented the sensitivity of PC cells to cisplatin by inhibiting the Wnt / beta-catenin pathway ."

eidos
"Jiang et al.18 pointed out that USP22 contributes to CRC cell stemness and decreases the sensitivity of CRC cells to chemoresistance via the Wnt / beta-Catenin pathway ."
USP22 affects c-NHEJ
| 3
USP22 activates c-NHEJ. 3 / 3
| 3

reach
"We demonstrate that Usp22 promotes c-NHEJ and CSR in vivo."

reach
"These results further suggest that Usp22 promotes the c-NHEJ but not the A-EJ pathway."

reach
"Early pro B ablation of Usp22 results in the blockade of B-cell development and defects in V to DJ recombination, supporting other findings that Usp22 promotes c-NHEJ."
| 1 2
| 1 2

reach
"Notably, USP22 knockout dramatically suppressed in vitro proliferation, colony formation; and angiogenesis, growth, metastasis of A549 and H1299 in mouse xenograft model, and significantly prolonged survival of metastatic cancer bearing mice."

eidos
"USP22 depletion decreased cell proliferation , migration , Vascular Mimicry ( VM ) formation , and angiogenesis ."

reach
"Knockdown of USP22 in an in vivo model was shown to decrease tumor angiogenesis, impair non-homologous DNA damage repair pathways and significantly improve the therapeutic efficacy of cisplatin."
USP22 affects USP14
| 3
| 3

reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."

reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."

reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
USP22 affects TNFRSF10B
| 3

sparser
"The fluorescence intensity of calcein-AM and rhodamine123 in the SW480-USP22 group were significantly increased when compared with that in the control cells (both P <0.01)."

sparser
"Results: CCK-8 assay showed that the IC 50 values of SW480-USP22 (SW480 cells overexpressing USP22) treated with oxaliplatin for 24 h and 48 h was (4.62±0.05)μmol/L and (2.32±0.04)μmol/L respectively; which was 2.7 times and 3.0 times higher than that in control cells, respectively."

sparser
"The protein expression levels of MRP1 and P-gp in SW480-USP22 cells were significantly increased when compared with that in the control cells(both P <0.01)."
USP22 affects Sirt1/JAK/STAT3
| 3
USP22 activates Sirt1/JAK/STAT3. 3 / 3
| 3

reach
"26 Xu et al suggested that miR-30e-5p suppresses NSCLC tumorigenesis by targeting ubiquitin carboxyl-terminal hydrolase 22 mediated Sirt1/JAK/STAT3 signaling."

reach
"In NSCLC, miR-30e-5p suppressed tumorigenesis and metastasis by inhibiting USP22-mediated Sirt1/JAK/STAT3 signaling."

reach
"MicroRNA-30e-5p suppresses non small cell lung cancer tumorigenesis by regulating USP22 mediated Sirt1/JAK/STAT3 signaling."
USP22 affects SUPT3H
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP22 affects STAT3
| 3
USP22 activates STAT3. 3 / 3
| 3

reach
"In conclusion, USP22 attenuated the invasion capacity of colon cancer cells by inhibiting the STAT3 and MMP9 signaling pathway."

reach
"Additionally, a recent publication showed that USP22 modulated the activity of STAT3 indirectly by stabilizing EGFR, which indicated that USP22 and USP28 may have redundant effects in NSCLC."

reach
"In colon cancer, USP22 was reported to attenuate the invasion capacity of colon cancer cells by inhibiting the STAT3 and MMP9 signaling pathway."
USP22 affects SHH
| 2 1
USP22 binds SHH.
| 1 1
| 1 1

sparser
"Through co-IP assay, we determined that the interaction between SHH and USP22 was disrupted by LINC01426 knockdown (Fig. xref and Fig. S xref )."

reach
"Through co-IP assay, we determined that the interaction between SHH and USP22 was disrupted by LINC01426 knockdown."
USP22 increases the amount of SHH.
| 1
USP22 increases the amount of SHH. 1 / 1
| 1

reach
"Ubiquitination assays manifested that LINC01426 and USP22 modulated SHH ubiquitination levels."
| 1 1
| 1 1

reach
"Silencing of either USP22 or RNF40 reduced short-term cell viability and clonogenic growth of osteosarcoma cells (Fig. 6A and B)."

eidos
"Significance : RNA demethylase ALKBH5 upregulates USP22 and RNF40 to inhibit histone H2A ubiquitination and induces expression of key replication and DNA repair-associated genes , driving osteosarcoma progression ."
USP22 affects OS tumor growth
| 3
USP22 activates OS tumor growth. 3 / 3
| 3

eidos
"In addition , downregulation of USP22 suppressed OS tumor growth and metastasis in vivo ."

eidos
"As expected , downregulation of USP22 suppressed OS tumor growth and metastasis in vivo ."

eidos
"These results suggest that USP22 downregulation inhibited OS tumor growth and metastasis in vivo ."
USP22 affects MKI67
| 2 1
USP22 increases the amount of MKI67.
| 2
USP22 increases the amount of MKI67. 2 / 2
| 2

reach
"Moreover, the depletion of USP22 decreased the levels of FASN and Ki-67 in mouse xenograft tumors, and exogenous FASN rescued those effects (Fig. 6H)."

reach
"Depletion of USP22 repressed the expression of the cell proliferation antigen Ki-67, and reconstituted expression of FASN rescued this effect (Fig. 6A)."
USP22 binds MKI67.
| 1
| 1

sparser
"Ki67 expression was associated with USP22 overexpression in cervical cancer, prostate cancer and oral squamous cell carcinoma [ xref , xref , xref ]."
USP22 affects MED1
| 3
USP22 binds MED1. 3 / 3
| 3

sparser
"The interaction between the endogenous USP22 and MED1 was further validated in mouse primary iNKT cells because MED1 was detected in anti-USP22 immunoprecipitates but not the normal rabbit IgG controls ( xref ), indicating a possibility that USP22 regulates iNKT cell development through, at least partially, MED1 interaction."

sparser
"USP22 interacts with MED1 in iNKT cells."

sparser
"Since USP22 interacts with MED1, both of which are transcription coactivators involved in promoting T-bet and IL-2R gene transcription in iNKT cells, we then asked whether MED1 binds to the promoters of T-bet and IL-2Rβ in a USP22-dependent manner, or vice versa."
USP22 affects LUAD
| 3
USP22 activates LUAD. 3 / 3
| 3

reach
"In this study, we speculated that USP22 might be involved in a variety of ways to promote the development of LUAD, including ubiquitination and immunosuppression."

reach
"In conclusion, we constructed a global regulation network to show that USP22 may promote the development of LUAD through ubiquitination and immunosuppression."

reach
"According to the USP22 comprehensive regulation network, we propose that USP22 may promote the development of LUAD through ubiquitination and immunosuppression."
USP22 affects H2Aub
| 3
USP22 deubiquitinates H2Aub.
| 2
USP22 deubiquitinates H2Aub. 2 / 2
| 2

reach
"However, whether deubiquitination of H2Aub (monoubiquitinated histone) by USP22 reverses the phenotype is not yet clearly established ."

reach
"USP22 deubiquitinates histone H2Bub and H2Aub."
USP22 activates H2Aub.
| 1
USP22 activates H2Aub. 1 / 1
| 1

reach
"Furthermore, USP22 can regulate DNA repair events by targeting the deubiquitination of proteins other than H2A (22, 23, 37, 45), it is possible that in addition to H2Aub, other USP22 target proteins may contribute to ALKBH5’s DNA repair and oncogenic functions."
USP22 affects FOXO1
| 3
USP22 activates FOXO1. 3 / 3
| 3

reach
"Western blot analysis of control and USP22-silenced GC cells showed that USP22 modulates the c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling pathways."

reach
"USP22 promotes GC progression by modulating FOXO1 or YAP signaling pathways via c-Myc/NAMPT/SIRT1."

reach
"Oncogenic USP22 supports gastric cancer growth and metastasis by activating c-Myc/NAMPT/SIRT1-dependent FOXO1 and YAP signaling."
USP22 affects FAM126A
| 3
USP22 activates FAM126A. 3 / 3
| 3

reach
"The USP22 increases growth and metastasis of HCC cells via inducing Wnt/β-catenin signaling."

reach
"Simply put, USP22 may activate the SIRT1–AKT–MRP1 pathway and consequently promote MDR in human HCC cells (226)."

reach
"Furthermore, we provided the evidence to show that knockdown of USP22 inhibited HCC growth in tumor-bearing nude mice."
USP22 affects Death
| 3
USP22 inhibits Death. 3 / 3
| 3

reach
"Ma et al. found that ubiquitin-specific peptidase 22 (USP22) inhibits cardiomyocyte death induced by ferroptosis in myocardial I/R injury via the SIRT1/p53/SLC7A11 axis, providing a novel therapeutic target for the treatment [83]."

reach
"Overexpression of USP22 could inhibit ferroptotic cardiomyocyte death to protect against IRI (102)."

reach
"A recent study shows that the expression of USP22 protein, a kind of deubiquitinase, can inhibit ferroptotic cardiomyocyte death through the SIRT1/p53/SLC7A11 axis and further protect against myocardial ischemia/reperfusion injury [64]."
USP22 affects DNA Damage
| 3
| 3

reach
"Knockdown of USP22 in an in vivo model was shown to decrease tumor angiogenesis, impair non-homologous DNA damage repair pathways and significantly improve the therapeutic efficacy of cisplatin."

reach
"According to that model, USP22 enhances DNA damage repair and cisplatin resistance by deubiquitinating histone H2A, which in turn facilitates the phosphorylation of histone H2AX."

reach
"The study reveal the dual mechanism of USP22 involvement in cisplatin resistance : (1) USP22 enhances DNA damage repair and induce cisplatin resistance by promoting the phosphorylation of histone H2AX via deubiquitinating histone H2A."

eidos
"As reported previously , USP22 promotes the proliferation of non-small cell lung cancer by regulating the ubiquitination of COX-221 ."
USP22 affects BAX
| 3
USP22 decreases the amount of BAX.
| 2
USP22 decreases the amount of BAX. 2 / 2
| 2

reach
"We found that USP22 silencing in A549 and NCI-H460 cells increased the protein expression of p53, p21 and Bax, the key p53 signal molecules (XREF_FIG A), suggesting that p53 activation plays a role in USP22 silencing induced growth inhibition."

reach
"USP22 knockdown in anaplastic thyroid carcinoma cells induces mitochondria-dependent apoptotic pathway by upregulating levels of apoptotic protein, Bax and Bid, and activating caspase-3 [6]."
USP22 activates BAX.
| 1
USP22 activates BAX. 1 / 1
| 1

reach
"Further analyses showed that USP22 silencing in HepG2 cells decreased the Bcl-2 and Bax ratio and enhanced the release of cytochrome c into the cytoplasm, suggesting the initiation of mitochondrial mediated apoptosis."
USP22 affects AR-FL
| 3
USP22 binds AR-FL. 3 / 3
| 3

reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."

reach
"In addition, the interaction of USP22 and AR (including AR-FL and AR-Vs) was also confirmed."

reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
USP14 affects USP22
| 3
| 3

reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."

reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."

reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
TNFRSF10B affects USP22
| 3

sparser
"The fluorescence intensity of calcein-AM and rhodamine123 in the SW480-USP22 group were significantly increased when compared with that in the control cells (both P <0.01)."

sparser
"Results: CCK-8 assay showed that the IC 50 values of SW480-USP22 (SW480 cells overexpressing USP22) treated with oxaliplatin for 24 h and 48 h was (4.62±0.05)μmol/L and (2.32±0.04)μmol/L respectively; which was 2.7 times and 3.0 times higher than that in control cells, respectively."

sparser
"The protein expression levels of MRP1 and P-gp in SW480-USP22 cells were significantly increased when compared with that in the control cells(both P <0.01)."
SUPT3H affects USP22
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
SOX2 affects USP22
| 3
SOX2 increases the amount of USP22. 3 / 3
| 3

reach
"USP22 is located directly on the Sox2 promoter and negatively regulates Sox2 transcription in ESCs [XREF_BIBR]."

reach
"USP22 is known to bind to the promoter region of Sox2 and negatively regulates Sox2 transcription in embryonic stem cells (ESCs) 47."

reach
"USP22 has been found to be located directly on the Sox2 promoter and catalyzes deubiquitination of H2B and attenuates Sox2 transcription."
RAS affects USP22
| 3
RAS activates USP22. 3 / 3
| 3

reach
"These findings suggest that SOS1/RAS and downstream ERK and PI3K/AKT pathways mediate the oncogenic role of USP22 in gastric cancer."

reach
"Furthermore, our study indicated that SOS1 was upregulated in USP22-overexpressing gastric cancer cells and xenograft tumor tissue, accompanied by activation of the RAS/ERK and PI3K/AKT pathways, suggesting that SOS1/RAS signaling mediates the oncogenic role of USP22 in gastric cancer."

reach
"These results suggest that SOS1/RAS signaling mediates the oncogenic role of USP22 in gastric cancer."
PI3K affects USP22
| 3
PI3K activates USP22. 3 / 3
| 3

reach
"Western blot analysis was conducted to detect the activation of RAS/ERK and PI3K/AKT signaling in USP22-overexpressing SGC7901 cells and xenograft tumor tissues."

reach
"These findings suggest that SOS1/RAS and downstream ERK and PI3K/AKT pathways mediate the oncogenic role of USP22 in gastric cancer."

reach
"Western blot analysis was conducted to detect the activation of RAS and ERK and PI3K and AKT signaling in USP22 overexpressing SGC7901 cells and xenograft tumor tissues."
NFATC2 affects USP22
2 | 1
2 | 1

No evidence text available

No evidence text available

reach
"Gao et al found that USP22 interacts with and deubiquitinates NFATc2, and also stabilizes NFATc2 protein and promotes NFATc2 function to facilitate IL-2 expression in T cells."
MED1 affects USP22
| 3
USP22 binds MED1. 3 / 3
| 3

sparser
"The interaction between the endogenous USP22 and MED1 was further validated in mouse primary iNKT cells because MED1 was detected in anti-USP22 immunoprecipitates but not the normal rabbit IgG controls ( xref ), indicating a possibility that USP22 regulates iNKT cell development through, at least partially, MED1 interaction."

sparser
"USP22 interacts with MED1 in iNKT cells."

sparser
"Since USP22 interacts with MED1, both of which are transcription coactivators involved in promoting T-bet and IL-2R gene transcription in iNKT cells, we then asked whether MED1 binds to the promoters of T-bet and IL-2Rβ in a USP22-dependent manner, or vice versa."
KPNA2 affects USP22
| 3
| 3

sparser
"Results from endogenous immunoprecipitation assays suggest that KPNA2 interacted with USP22 constitutively but interacted with IRF3 or pIRF3 in THP-1 cells in a manner dependent on viral infection ( xref )."

sparser
"In contrast, mutation of USP22 NLS (USP22-RR/AA) did not affect its association with KPNA2 ( xref ), suggesting that USP22 interacts with KPNA2 independently of its NLS."

sparser
"In our study, we found that knockout of USP22 impaired virus-triggered nuclear translocation of p65 and induction of p65-target genes such as Tnf and Il6 , which was restored by reconstitution of KPNA2, suggesting a role of the USP22KPNA2 axis in NF-κB activation after viral infection (data not shown)."
AR-V7 affects USP22
| 3
USP22 binds AR-V7. 3 / 3
| 3

reach
"Unlike rutaecarpine, nobiletin failed to alter the GRP78-mediated degradation of AR-V7.In conclusion, this research not only demonstrates the reason why nobiletin suppressed the growth process of CRPC through the selective degradation of AR-V7, but also enriches our understanding of the degradation mechanism of AR-V7 and provides an efficient treatment target to overcome CRPC via targeting the interaction between AR-V7 and USP14/USP22 (Fig. 7G)."

reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."

reach
"We confirmed the endogenous interaction between AR-V7 and USP22."
AR-FL affects USP22
| 3
USP22 binds AR-FL. 3 / 3
| 3

reach
"However, it is worth noting that nobiletin had no effect on the interactions between AR-FL and USP14/USP22, which may explain why nobiletin has a certain selectivity in inducing the degradation of AR-V7.Our previous study has been demonstrated that rutaecarpinecan selectively trigger the GRP78-dependent AR-V7 degradation [23]."

reach
"In addition, the interaction of USP22 and AR (including AR-FL and AR-Vs) was also confirmed."

reach
"Immunofluorescence and western blot experiments showed that these molecular events mainly occurred in the nucleus.We also confirmed that nobiletin can significantly decrease the interactions between AR-V7 and USP14/USP22 in a time and concentration-dependent manner, but did not affect the interactions between AR-FL and USP14/USP22, which may explain why nobiletin exhibits a certain selectivity in inducing the degradation of AR-V7."
| 3

reach
"After the mice injected with Bel/Fu cells with siRNA interference of USP22 expression were treated with 5-FU, the size of the subcutaneous xenografts significantly decreased, suggesting that downregulation of USP22 expression mitigated 5-FU resistance and increased the sensitivity of HCC to chemotherapy drugs, which may be related to the physiological function of USP22 to form a complex with BMI1."

reach
"After the Bel/Fu cells were injected into nude mice, the mean diameter of the subcutaneous xenografts that developed was 1.5 cm, whereas for mice injected with Bel/Fu cells with stable expression of USP22 siRNA, the mean diameter was smaller (1.4 cm, n = 6, P < 0.05, XREF_FIG); after the mice injected with Bel/Fu cells were treated with 5-FU, the mean diameter of xenografts was smaller (1.2 cm, n = 6, P < 0.05, XREF_FIG); after the mice injected with Bel/Fu cells with stable expression of USP22 siRNA were treated with 5-FU, the mean diameter of xenografts was 0.9 cm, significantly smaller than that observed in mice injected with Bel/Fu cells alone (n = 6, P < 0.05, XREF_FIG)."

reach
"Remarkably, silencing USP22 reduced the tumor volume of BEL/FU cells treated with 5-FU (BEL/FU control shRNA cells treated with 5-FU vs BEL/FU USP22 shRNA treated with 5-FU, 945 +/-545mm 3 vs 372 +/-228mm 3, P < 0.05)."

reach
"Whereas, in p53-deficient CRC cells, ROS-mediated inhibition of USP22 is relieved, leading to FASN stabilization, which thus promotes lipid synthesis and tumor growth."

reach
"Whereas, in p53-deficient CRC cells, relief of ROS-mediated USP22 repression promotes FASN stabilization and lipid accumulation, and thus promotes tumorigenesis (Fig. 7D)."
2 |
Hsa-miR-6825-5p decreases the amount of USP22. 2 / 2
2 |

No evidence text available

No evidence text available
Cisplatin affects USP22
| 2
Cisplatin decreases the amount of USP22. 2 / 2
| 2

reach
"A recent study suggested that cisplatin can suppress the expression of USP22 through p38 and MAPK pathway in HeLa cells."

reach
"Cisplatin, the activator of p38 MAPK, also suppressed USP22 expression."
CircFAT1 affects USP22
| 2
CircFAT1 decreases the amount of USP22. 2 / 2
| 2

reach
"We also found that overexpression of miR-30e-5p and knockdown of circFAT1 (e2) significantly reduced the mRNA levels of USP22."

reach
"Using a series of experiments, we found that circFAT1 (e2) knockdown decreased the expression level of USP22 through sponging miR-30e-5p."
YAP1 affects USP22
| 1 1
| 1 1

sparser
"Using IP assays, USP22 interaction with YAP at the endogenous level in A375 melanoma cells was observed ( xref )."

reach
"The interaction between USP22 and KDM3A and between KDM3A and YAP1 was further validated."
USP51 affects USP22
| 2
| 2

sparser
"To test this idea, we expressed wild type (WT) or mutant forms of USP22, USP27X and USP51 in which a conserved cysteine required for activity in USP22 is changed to serine in 293T cells ( xref )."

sparser
"To test this idea, we expressed wild-type (WT) or mutant forms of USP22, USP27X, and USP51 in which a conserved cysteine required for activity in USP22 is changed to serine in 293T cells ( Figures 3 A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 affects ubH2B
| 2
USP22 deubiquitinates ubH2B. 2 / 2
| 2

reach
"Deubiquitination of ubH2B is catalyzed by the ubiquitin protease subunit of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) transcriptional coactivator complex : Nonstop (FBgn0013717) in Drosophila melanogaster, Ubp8 in Saccharomyces cerevisiae, and USP22 in humans."

reach
"While other events, such as histone exchange or direct or indirect RNF20 inactivation, are also possible, studies in the lab are ongoing to determine if USP22 (the mammalian homolog to Ubp8) also deubiquitinates ubH2B."
USP22 affects tumor growth
| 1
USP22 activates tumor growth. 1 / 2
| 1

eidos
"Moreover , the DUB USP7 , USP13 , USP22 , USP28 , USP36 and USP37 stabilize c-Myc , thereby stimulating tumor growth [ 155 , 157 , 171-174 ] ."
| PMC
USP22 affects sensitivity PC cells cisplatin
| 2
USP22 inhibits sensitivity PC cells cisplatin. 2 / 2
| 2

eidos
"Inhibition of USP22 reduced the cell stemness and augmented the sensitivity of PC cells to cisplatin by inhibiting the Wnt / beta-catenin pathway ."

eidos
"Downregulation of USP22 raised the sensitivity of PC cells to cisplatin , reduced the levels of stem cell markers , reduced the tumor sphere formation and migration , and promoted apoptosis ."
USP22 affects repair
| 2
USP22 activates repair. 2 / 2
| 2

eidos
"USP22 promotes DSB repair via HR DSBs are repaired by HR in the S / G2 phase of the cell cycle and involves assembly of BRCA1 , BRCA2 , PALB2 , and Rad51 ."

eidos
"USP22 modulates DNA repair factor expression and survival after DNA damage While initial studies identified USP22 as a modulator of AR and MYC , the overall mechanisms by which USP22 promotes disease progression remain unclear ."
USP22 affects proteolysis
| 2
USP22 inhibits proteolysis.
| 1
| 1

reach
"Lastly, ubiquitylation of USP22 mediated by the anaphase promoter complex and cyclosome (APC/C) induces USP22 protein degradation during the cell cycle [XREF_BIBR]."
USP22 activates proteolysis.
| 1
| 1

reach
"Mechanistically, PRDM1 enhances USP22 transcription, thus reducing SPI1 protein degradation through deubiquitination, which enhances PD-L1 transcription."
USP22 affects pathway
| 2
USP22 activates pathway. 2 / 2
| 2

sparser
"In CRC, because of the low expression of miR-30-5p, USP22 activates the Wnt/β-catenin pathway by increasing the nuclear concentration of β-catenin, and enhancing cancer stemness and tumorigenesis [ xref ]."

sparser
"By up- and downregulation of USP22 expression, we also proved that USP22 can activate the Wnt/β-Catenin pathway, which in turn affected the proliferation and migration of HepG2 cells."
USP22 affects melanoma BRAF resistance
| 2
USP22 inhibits melanoma BRAF resistance. 2 / 2
| 2

eidos
"USP22 promotes melanoma and BRAF inhibitor resistance via YAP stabilization Yes-associated protein ( YAP ) is a conserved transcriptional coactivator that plays key roles in controlling organ size , tumorigenesis and drug resistance ."

eidos
"USP22 promotes melanoma and BRAF inhibitor resistance via YAP stabilization ."
USP22 affects hydrolase
| 2
| 2

reach
"Interestingly, the human and fly SAGA complexes possess a module that houses ubiquitin hydrolase activity mediated by the USP22 (human) and Nonstop (fly) proteins."

reach
"As suspected from its domain structure, USP22 is able to hydrolyze a ubiquitin linkage from histone H2B in vitro and endogenous USP22 contributes ubiquitin hydrolase activity to the hSAGA complex."
USP22 affects hSAGA
| 2
USP22 activates hSAGA. 2 / 2
| 2

reach
"Confirming a functional role for USP22 within hSAGA, we show that endogenous USP22 contributes deubiquitylating activity to hSAGA."

reach
"As an example, the protocol was adapted from one used by Zhao et al. to isolate the USP22 module of the human TFTC, STAGA, and hSAGA complex [XREF_BIBR]."
USP22 affects growth
| 2
USP22 inhibits growth. 2 / 2
| 2

sparser
"Genetic depletion of USP22 inhibited liver cancer growth in an immune system-dependent manner, increased tumor immunogenicity and tumor-infiltrating lymphocytes, and improved therapeutic efficacy of CD274-targeted immunotherapy and CDDP-based chemotherapy in mice."

sparser
"Additionally, knockdown of USP22 inhibited gastric cancer xenografts growth."
USP22 affects ferroptosis-induced myocardial cell death
| 2
USP22 inhibits ferroptosis-induced myocardial cell death. 2 / 2
| 2

eidos
"The above results indicated that USP22 elevation inhibited ferroptosis-induced myocardial cell death ."

eidos
"USP22 elevation inhibits ferroptosis-induced myocardial cell death ."

reach
"In addition, we find that USP22 promotes de novo fatty acid synthesis and contributes to HCC tumorigenesis, however, this tumorigenicity is suppressed by inhibiting the expression of PPARγ, ACLY, or ACC in in vivo tumorigenesis experiments."

reach
"In p53 wild-type colorectal cancer (CRC) cells, hydrogen peroxide (H 2 O 2 )-induced p53 expression represses the transcription of deubiquitinase USP22, which otherwise deubiquitinates and stabilizes Fatty Acid Synthase (FASN), and thus inhibits fatty acid synthesis."

reach
"Moreover, USP22 promotes both HR (23) and NHEJ (48, 59)."

eidos
"Moreover , USP22 promotes both HR ( 23 ) and NHEJ ( 48 , 59 ) ."

reach
"Gain- and loss-of-function assays showed that USP22 promoted gastric cancer cell growth and cell cycle transition while suppressing apoptosis in vitro."

reach
"Our results indicate that USP22 promotes cell proliferation, migration, invasion, and cell cycle transition, while inhibiting apoptosis in gastric cancer cells."
| 2

reach
"Our study also shows that USP22 silencing in GC cells decreases cell proliferation and induces cell cycle arrest and apoptosis in vitro, and suppresses tumor growth and metastasis in vivo."

reach
"Therefore, up-regulation of USP22 expression will lead to abnormal activation of multiple pathways to promote cell survival while down-regulation of USP22 expression can induce cell cycle arrest at G0/G1 phase in different types of cancer cells (Zhang et al., 2008)."
USP22 affects cell apoptosis
| 1
USP22 activates cell apoptosis. 1 / 2
| 1

eidos
"Accordingly , USP22 downregulation also attenuated cerebral I / R-induced oxidative stress , inflammation , and cell apoptosis in mice , thereby reducing nerve injury and neurological dysfunction [ 20 ] ."
USP22 affects UBC
| 2
USP22 increases the amount of UBC. 2 / 2
| 2

reach
"It suggested that knocking down USP22 may up-regulate the expression of UBC to promote the pathways of cell cycle and ubiquitin mediated proteolysis in the development of LUAD."

reach
"We confirmed that USP22 could induce the expression of UBC to inhibit the cell cycle, lysosomal degradation and ubiquitin mediated proteolysis [XREF_BIBR], which could further promote the occurrence and development of LUAD."
USP22 affects TGFB
| 2
Modified USP22 increases the amount of TGFB. 2 / 2
| 2

reach
"Moreover, USP22 overexpression can promote EMT and TGF-beta expression, whereas USP22 knockdown can reverse EMT and reduce the metastasis of lung adenocarcinomas."

reach
"Moreover, USP22 overexpression can promote EMT and TGF-beta expression, whereas depletion of USP22 can reverse EMT and reduce metastasis of lung adenocarcinomas."
USP22 affects TBX21
| 2
| 2

sparser
"Indeed, the binding of USP22 to the promoters of both T-bet and IL-2Rβ gene was detected by chromatin immunoprecipitation (ChIP) assay ( xref )."

sparser
"Notably, MED1 knockdown significantly reduced the levels of USP22 binding to both T-bet and IL-2Rβ promoters ( xref )."
USP22 affects TAF10
2 |
2 |

No evidence text available

No evidence text available
USP22 affects TADA3
2 |
2 |

No evidence text available

No evidence text available
USP22 affects SGF29
2 |
2 |

No evidence text available

No evidence text available
USP22 affects RNF20
| 2
| 2

sparser
"Future studies should also examine the mechanism by which the transcriptional regulations of RNF20 and USP22 interact."

sparser
"To determine the association of USP22, H2Bub1 and RNF20 protein expression with CICs, we measured the expression level of these proteins in both CD133+ and CD133− cells."
USP22 affects RIC3
2 |
2 |

No evidence text available

No evidence text available
USP22 affects RAD51
| 2
| 2

reach
"To assay for this we used the U2OS cell line and overexpressed either FLAG-H2B or FLAG-H2B and analyzed recruitment of GFP-USP22, Rad51, PALB2, and BRCA2 after induction of mCherry-LacI-FOKI (Figure 2d,e)."

reach
"Given that USP22 KD causes moderate increase in global H2Bk120ub and the data show both USP22 and H2BK120ub are clearly important for recruitment of USP22, Rad51, PALB2, and BRCA2 to sites of DSBs, this suggests the modulation and fine tuning of H2Bk120ub is important."
USP22 affects OS cell
| 2
USP22 activates OS cell. 2 / 2
| 2

eidos
"We also suggested that downregulation of USP22 inhibited OS cell proliferation and invasion in vitro ."

eidos
"USP22 downregulation inhibited OS cell proliferation , invasion , and epithelial-mesenchymal transition ( EMT ) in vitro ."
USP22 affects NT5E
2 |
2 |

No evidence text available

No evidence text available
USP22 affects NPC
| 2
USP22 activates NPC. 2 / 2
| 2

reach
"USP22 promotes the proliferation of NPC."

reach
"By contrast, USP22 was overexpressed in NPC cells and promoted the proliferation of NPC."
USP22 affects NLRP3 inflammasome
| 2
USP22 inhibits NLRP3 inflammasome. 2 / 2
| 2

eidos
"Here , we demonstrated that USP22 ( ubiquitin specific peptidase 22 ) promotes NLRP3 degradation and inhibits NLRP3 inflammasome activation ."

eidos
"Mechanistically , USP22 inhibits NLRP3 inflammasome activation via the promotion of ATG5-mediated macroautophagy / autophagy ."
USP22 affects MINDY2
2 |
2 |

No evidence text available

No evidence text available
USP22 affects MAP2K6
| 2
| 2

sparser
"Furthermore, the direct interaction between USP22 and MKK6 promoter was detected by chromatin immunoprecipitation (ChIP) assay."

sparser
"USP22 could interact directly with MKK6 promoter."
USP22 affects LYPD3
2 |
2 |

No evidence text available

No evidence text available
USP22 affects KDM3A
| 1 1
| 1 1

reach
"The interaction between USP22 and KDM3A and between KDM3A and YAP1 was further validated."

sparser
"The interaction between USP22 and KDM3A and between KDM3A and YAP1 was further validated."
USP22 affects IKBKB
| 2
USP22 inhibits IKBKB. 2 / 2
| 2

reach
"Importantly, we observed that USP18 and USP22, but not USP14, may directly inhibit IKK-beta activation through an NLRC5 independent mechanism."

reach
"They show that three USPs -- USP14, USP18, and USP22 -- fulfilled these criteria, but focused on USP14, as USP18 and USP22 could also inhibit IKKbeta activation directly in the absence of NLRC5."
USP22 affects IFN-λ1
| 2
USP22 decreases the amount of IFN-λ1. 2 / 2
| 2

reach
"Nat Rev Immunol 21, 852 548-569, doi:10.1038/s41577-021-00524-z (2021These findings suggest that USP22 negatively regulates IFN-λ1 expression and ISG 232 induction."
| DOI

reach
"Mean and SD of three independent experiments in triplicate USP22 negatively regulates STAT1 signaling and IFN-λ1 expression."
| DOI
USP22 affects H2BK120ub
| 2
USP22 deubiquitinates H2BK120ub. 2 / 2
| 2

reach
"USP22 is involved in the deubiquitylation of H2BK120ub, a mark that is found at DSB sites, USP22 could be a “reader” for this mark and potentiate the recruitment of other DNA damage factors through this ubiquitin mark."

reach
"Other major DUBs with specificity for histone H2AK119ub over H2BK120ub are BAP1 and USP16, while USP3, USP12, USP22, and USP44 deubiquitinate both H2AK119ub and H2BK120ub, as well as different non histone substrates [XREF_BIBR]."
USP22 affects H2AC20
1 | 1
1 | 1

No evidence text available

sparser
"Subsequent immunoprecipitation (IP) experiments confirmed that USP22 bind to endogenous H2A in A549 cell line (Figures xref )."
USP22 affects GC
| 2
USP22 activates GC. 2 / 2
| 2

reach
"MiR-4490 regulates USP22 mediated GC growth and metastasis in vivo."

reach
"To generate mir-4490 and USP22-co-expressing cells, 3ml of a concentrated USP22 lentiviral expression vector solution was added to miR-4490 overexpressing GC cells as described previously."
USP22 affects EZH2
| 1 1
USP22 inhibits EZH2. 2 / 2
| 1 1

eidos
"EZH2 elevation aggravated the cardiac injury in SIMD rats , while USP22 upregulation inhibited the effect of EZH2 , which reduced the cardiac injury in SIMD rats ."

reach
"EZH2 elevation aggravated the cardiac injury in SIMD rats, while USP22 upregulation inhibited the effect of EZH2, which reduced the cardiac injury in SIMD rats."
USP22 affects ESR1
| 2
USP22 activates ESR1. 2 / 2
| 2

reach
"USP22 enhances ERalpha induced transactivation."

reach
"USP22 positively modulates ERalpha action via its deubiquitinase activity in breast cancer."
USP22 affects E2F6
| 1 1
| 1 1

sparser
"Therefore, these findings provide mechanistic insights into the USP22-mediated control of oncogenic AKT signaling, emphasizing the importance of USP22-E2F6 regulation in HCC development."

reach
"USP22 interacts with and stabilizes E2F6, resulting in the transcriptional repression of phosphatase DUSP1."

eidos
"] Our previous work revealed that USP22 was able to promote HCC stemness by a HIF1alpha / USP22 positive feedback loop and mediate multidrug resistance ( MDR ) by activating the SIRT1 / AKT / MRP1 pathway ."

eidos
"Our previous research showed that ubiquitin specific peptidase 22 ( USP22 ) induces multidrug resistance of HCC via the Sirtuin 1 ( SIRT1 ) / AKT / multidrug resistance associated protein 1 ( MRP1 ) signaling pathway151 ; and recently we also explored the relationship among USP22 , sorafenib resistance , and cancer stemness.152 Precision therapy is the future direction of cancer treatment ."
USP22 affects DSB repair
| 2
USP22 activates DSB repair. 2 / 2
| 2

reach
"Conceivably, reduced USP22 expression inducing DSB repair defects may lead to chromosomal rearrangements in addition to the numerical chromosome changes identified in this study."

reach
"If the function of USP22 in DSB repair is conserved in other cell types, then the loss of USP22 may prevent correct DSB repair and promote the accumulation of pathologic mutations underlying the development of cancer."
USP22 affects DNA repair
| 2
| 2

reach
"It is likely that changes in USP22 and RNF40 status due to altered levels of m A may direct the DNA repair machinery to employ or not employ HR or NHEJ to repair damaged DNA."

reach
"Furthermore, USP22 can regulate DNA repair events by targeting the deubiquitination of proteins other than H2A (22, 23, 37, 45), it is possible that in addition to H2Aub, other USP22 target proteins may contribute to ALKBH5’s DNA repair and oncogenic functions."
USP22 affects CRPC
| 2
USP22 activates CRPC. 2 / 2
| 2

reach
"Given the ability of USP22 to enhance AR accumulation, AR activity, and CRPC, the biological impact of a model of tetracycline inducible shUSP22 was developed in therapy sensitive PCa cells."

reach
"USP22 promotes CRPC through enhanced ligand independent and androgen stimulated AR transcriptional activity and sustained AR activity in the presence of antagonists, concomitant with AR protein accumulation."
USP22 affects CRC
| 2
USP22 activates CRC. 2 / 2
| 2

reach
"However, the mechanism by which USP22 promotes CRC metastasis remains largely unknown."

reach
"In addition, Usp22 promotes CRC by stabilizing cyclin B1."
USP22 affects CDK1
1 | 1
1 | 1

No evidence text available

sparser
"From our proteomic analysis, we noticed that CCNB1 appears to form a complex with both USP22 and CDK1; this prompted us to ask whether CDK1 phosphorylates USP22."
USP22 affects CDH2
| 2
USP22 decreases the amount of CDH2. 2 / 2
| 2

reach
"AP4 down-regulation partially reversed the increases in N-cadherin and vimentin expression levels induced by USP22 up-regulation; however, no changes in USP22 expression levels were observed."

reach
"USP22 downregulation significantly increased the expression of E-cadherin (epithelial marker) but decreased the expression of N-cadherin and vimentin (mesenchymal markers) (XREF_FIG)."
USP22 affects CDC23
2 |
2 |

No evidence text available

No evidence text available
USP22 affects CD1B
2 |
2 |

No evidence text available

No evidence text available
USP22 affects BRD4
| 1 1
| 1 1

sparser
"AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4."

reach
"AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4."
USP22 affects BIRC5
| 1
USP22 increases the amount of BIRC5. 1 / 2
| 1

reach
"Subsequently, it was demonstrated that USP22 knockdown inhibited the growth of an RCC cell line ACHN and downregulated the protein level of survivin, accompanied by an increased level of cleaved-caspase-3."
USP22 affects AR-V7 protein
| 2
USP22 activates AR-V7 protein. 2 / 2
| 2

reach
"Our CHX-tracking assay confirmed that USP22 promoted the stability of AR-V7 protein."

reach
"Our current research focuses on the regulation of AR-V7 protein stability mediated by USP22."
USP22 affects ALKBH5
| 2
USP22 activates ALKBH5. 2 / 2
| 2

reach
"We performed rescue experiments to test whether ALKBH5’s tumor-promoting function may be mediated by USP22 and RNF40."

reach
"Furthermore, USP22 can regulate DNA repair events by targeting the deubiquitination of proteins other than H2A (22, 23, 37, 45), it is possible that in addition to H2Aub, other USP22 target proteins may contribute to ALKBH5’s DNA repair and oncogenic functions."
USP22 affects AKT1
| 1
USP22 activates AKT1. 1 / 2
| 1

reach
"Activation of ERK1/2 kinase rather than AKT1 by USP22 was found to be one of the mechanisms promoting LC3 processing."
USP22 affects ADR
| 2
USP22 inhibits ADR. 2 / 2
| 2

reach
"As we previously described, USP22 silencing increased the concentration of intracellular ADR."

reach
"In addition, overexpression of USP22 also reduced the intracellular ADR concentration in BEL7402 cells."
| 2

reach
"USP22 knockdown enhanced chemosensitivity of hepatocellular carcinoma cells to 5-Fu by up-regulation of Smad4 and suppression of Akt."

reach
"We also found that USP22 knockdown enhanced the anti-growth and pro apoptotic effect of 5-Fu in Bel/Fu cells."
TGFB1 affects USP22
| 1 1
| 1 1

sparser
"Therefore, our findings indicated that lung adenocarcinoma exhibiting nuclear USP22 expression was associated with increased TGF-β1, metastatic potential and poor survival outcomes."

reach
"The association between the USP22, TGF-beta1 and clinicopathologic parameters was tested using the chi-square tests."
TBX21 affects USP22
| 2
| 2

sparser
"Indeed, the binding of USP22 to the promoters of both T-bet and IL-2Rβ gene was detected by chromatin immunoprecipitation (ChIP) assay ( xref )."

sparser
"Notably, MED1 knockdown significantly reduced the levels of USP22 binding to both T-bet and IL-2Rβ promoters ( xref )."
TAF10 affects USP22
2 |
2 |

No evidence text available

No evidence text available
TADA3 affects USP22
2 |
2 |

No evidence text available

No evidence text available
SHH affects USP22
| 1 1
| 1 1

sparser
"Through co-IP assay, we determined that the interaction between SHH and USP22 was disrupted by LINC01426 knockdown (Fig. xref and Fig. S xref )."

reach
"Through co-IP assay, we determined that the interaction between SHH and USP22 was disrupted by LINC01426 knockdown."
SGF29 affects USP22
2 |
2 |

No evidence text available

No evidence text available
RNF20 affects USP22
| 2
| 2

sparser
"Future studies should also examine the mechanism by which the transcriptional regulations of RNF20 and USP22 interact."

sparser
"To determine the association of USP22, H2Bub1 and RNF20 protein expression with CICs, we measured the expression level of these proteins in both CD133+ and CD133− cells."
RIC3 affects USP22
2 |
2 |

No evidence text available

No evidence text available
RAD51 affects USP22
| 2
| 2

reach
"To assay for this we used the U2OS cell line and overexpressed either FLAG-H2B or FLAG-H2B and analyzed recruitment of GFP-USP22, Rad51, PALB2, and BRCA2 after induction of mCherry-LacI-FOKI (Figure 2d,e)."

reach
"Given that USP22 KD causes moderate increase in global H2Bk120ub and the data show both USP22 and H2BK120ub are clearly important for recruitment of USP22, Rad51, PALB2, and BRCA2 to sites of DSBs, this suggests the modulation and fine tuning of H2Bk120ub is important."
NT5E affects USP22
2 |
2 |

No evidence text available

No evidence text available
MIR101-1 affects USP22
| 2
| 2

reach
"XREF_BIBR reported that miR-101 reduces PTC cell proliferation, apoptosis resistance, migration, and invasion in vitro and suppresses tumor growth and metastasis in vivo by targeting USP22."

reach
"Furthermore, it was reported that miR-101 was markedly downregulated in papillary thyroid carcinoma tissues, and attenuated tumor growth in vitro by targeting Rac1 [XREF_BIBR] or USP22 [XREF_BIBR]."
MINDY2 affects USP22
2 |
2 |

No evidence text available

No evidence text available
MAP2K6 affects USP22
| 2
| 2

sparser
"Furthermore, the direct interaction between USP22 and MKK6 promoter was detected by chromatin immunoprecipitation (ChIP) assay."

sparser
"USP22 could interact directly with MKK6 promoter."
LYPD3 affects USP22
2 |
2 |

No evidence text available

No evidence text available
KDM3A affects USP22
| 1 1
| 1 1

reach
"The interaction between USP22 and KDM3A and between KDM3A and YAP1 was further validated."

sparser
"The interaction between USP22 and KDM3A and between KDM3A and YAP1 was further validated."
H2AC20 affects USP22
1 | 1
1 | 1

No evidence text available

sparser
"Subsequent immunoprecipitation (IP) experiments confirmed that USP22 bind to endogenous H2A in A549 cell line (Figures xref )."
E2F6 affects USP22
| 1 1
| 1 1

sparser
"Therefore, these findings provide mechanistic insights into the USP22-mediated control of oncogenic AKT signaling, emphasizing the importance of USP22-E2F6 regulation in HCC development."

reach
"USP22 interacts with and stabilizes E2F6, resulting in the transcriptional repression of phosphatase DUSP1."
CDC23 affects USP22
2 |
2 |

No evidence text available

No evidence text available
CDC20 affects USP22
| 2
CDC20 inhibits USP22. 2 / 2
| 2

reach
"In contrast, the APC and CDC20 E3 ligase complex negatively regulates USP22 activity by targeting it for degradation, presumably allowing CCNB1 downregulation so that cells can exit mitosis and enter anaphase."

reach
"Therefore, APC and CDC20 E3 ligase complex promotes USP22 protein degradation, presumably allowing CCNB1 degradation for cells to exit M phase."
CD1B affects USP22
2 |
2 |

No evidence text available

No evidence text available
BRD4 affects USP22
| 1 1
| 1 1

sparser
"AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4."

reach
"AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4."
Atx7 affects USP22
| 2
Atx7 inhibits USP22. 2 / 2
| 2

reach
"The mutation of the zinc finger domain in Atx7 that disrupts its interaction with USP22 dramatically abolishes sequestration of USP22."

reach
"Moreover, polyQ expansion of Atx7 decreases the deubiquitinating activity of USP22 and, consequently, increases the level of monoubiquitinated H2B."
ATXN7L3 affects AR
| 2
USP22 binds ATXN7L3 and AR. 2 / 2
| 2

sparser
"To further investigate this hypothesis, we analyzed putative interactions of USP22 or ATXN7L3 with AR in mammalian cells."

sparser
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR-dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
ATF3 affects USP22
| 2
ATF3 inhibits USP22. 2 / 2
| 2

eidos
"In summary , our results demonstrate that USP22 expression is promoted by AP2 and c-Myc and is suppressed by SP1 and ATF3 at the transcriptional level ."

eidos
"Besides AP2 , we found that ATF3 , a member of CREB protein family of transcription factors may suppress USP22 gene expression , and it seems ATF3 may possess an opposite transcriptional role of the previously reported CREB1 in USP22 expression [ 21 ] ."
AR affects ATXN7L3, and USP22
| 2
USP22 binds ATXN7L3 and AR. 2 / 2
| 2

sparser
"To further investigate this hypothesis, we analyzed putative interactions of USP22 or ATXN7L3 with AR in mammalian cells."

sparser
"This result together with the observed interaction between the AR and both ATXN7L3 and USP22 suggested that these proteins are recruited together to the promoters of AR-dependent genes upon ligand ind[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
APC affects USP22
| 2
APC inhibits USP22. 2 / 2
| 2

reach
"In contrast, the APC and CDC20 E3 ligase complex negatively regulates USP22 activity by targeting it for degradation, presumably allowing CCNB1 downregulation so that cells can exit mitosis and enter anaphase."

reach
"Therefore, APC and CDC20 E3 ligase complex promotes USP22 protein degradation, presumably allowing CCNB1 degradation for cells to exit M phase."

reach
"The association between USP22 and AP4 and liver, but not lymph node, metastasis may be due to these proteins driving blood stream, but not lymphatic, metastasis of CRC cells."

reach
"Consistent with the above results, ChIP analysis revealed that USP22 binds the promoter region of AP4."
1 |
Streptozocin increases the amount of USP22. 1 / 1
1 |

No evidence text available

reach
"USP 22, KDM3A, and YAP1 were found to be down-regulated in MI/RI and SPC protected MI/RI rats, as evidenced by up-regulated expressions of USP22, KDM3A, and YAP1, reduced pathological injury in the myocardium, myocardial infarction areas, apoptosis, and levels of CK-MB, cTnI, and LDH, and enhanced H9c2 cell viability; while the protective effects of Sevo were counteracted by silencing of USP22, KDM3A, and SPC upregulated USP22, which stabilized KDM3A protein levels via deubiquitination, and KDM3A inhibited histone 3 lysine 9 di-methylation (H3K9me2) levels in the YAP1 promoter to encourage YAP1 transcription, to reduce MI/RI."
Small hairpin RNA affects USP22
| 1
Small hairpin RNA increases the amount of USP22. 1 / 1
| 1

reach
"XREF_BIBR - XREF_BIBR Zhang and colleagues have demonstrated that ectopic overexpression of USP22 promotes cell proliferation and that suppression of USP22 expression by small hairpin RNA induces cell cycle arrest in human lung cancer cells."
Released shUSP22 affects USP22
| 1
Released shUSP22 inhibits USP22. 1 / 1
| 1

eidos
"iii ) The released shUSP22 enters the nucleus for transcription to specifically degrade USP22 mRNA and further suppress USP22 expression ."
Reconstitution PAM-mutated WT mutant USP22 cells affects USP22
| 1
Reconstitution PAM-mutated WT mutant USP22 cells activates USP22. 1 / 1
| 1

eidos
"Stable reconstitution of PAM-mutated WT and mutant USP22 in USP22 KO HT-29 cells restored USP22 expression ( Fig 1E , Appendix Fig S2A and B ) ."
1 |
Pirinixic acid increases the amount of USP22. 1 / 1
1 |

No evidence text available
Peptide affects USP22
| 1
| 1

eidos
"Cells treated with the cyclic peptide inhibitors had increased H2B-Ub levels , indicating that the peptides can also inhibit USP22 in vivo ."
Near % affects USP22
| 1
Near % inhibits USP22. 1 / 1
| 1

eidos
"Western blot analysis indicated that infection with the lentivirus for UPS22-specifc shRNA reduced the relative levels of USP22 expression by near 75 % ( Figure 4A , B ) ."
MiRNA-329-3p affects USP22
| 1
MiRNA-329-3p inhibits USP22. 1 / 1
| 1

eidos
"Mechanistically , miRNA-329-3p reduces USP22 expression to suppress beta-catenin signaling and improve prognosis of HCC ."
MiR-6886-3p affects USP22
| 1
MiR-6886-3p inhibits USP22. 1 / 1
| 1

reach
"MiR-6825-5p, miR-6845-5p, and miR-6886-3p were down-regulated by HULC, resulting in the elevation of Sirt1, USP22, and protective autophagy, thus attenuating the sensitivity of HCC cells to chemotherapeutic agents [82]."
MiR-144-3p affects USP22
| 1
USP22 binds miR-144-3p. 1 / 1
| 1

reach
"The interaction between miR-144-3p and USP22 was validated by dual-luciferase reporter assay."
Infection lentivirus UPS22-specifc shRNA affects USP22
| 1
Infection lentivirus UPS22-specifc shRNA inhibits USP22. 1 / 1
| 1

eidos
"Western blot analysis indicated that infection with the lentivirus for UPS22-specifc shRNA reduced the relative levels of USP22 expression by near 75 % ( Figure 4A , B ) ."
1 |
Hsa-miR-6893-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6876-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-6782-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
Hsa-miR-637 affects USP22
1 |
Hsa-miR-637 decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-485-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-483-3p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4728-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4524b-3p decreases the amount of USP22. 1 / 1
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No evidence text available
1 |
Hsa-miR-4433b-3p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-4252 decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3926 decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3680-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3612 decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-328-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3179 decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-3154 decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-29c-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-183-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-127-5p decreases the amount of USP22. 1 / 1
1 |

No evidence text available
Foci affects USP22
| 1
USP22 binds foci. 1 / 1
| 1

sparser
"Interestingly, immunostaining revealed that USP22 formed large nuclear foci that co-localized with PML bodies in telomerase-positive cells as well as in ALT cells, suggesting that USP22 is a constitutive component of PML bodies (Figure xref )."
| 1
Anthracycline decreases the amount of USP22. 1 / 1
| 1

reach
"Recently, Pirarubicin (4’-O-tetrahydropyranyl doxorubicin, THP), an anthracycline (analogue of another chemotherapeutic agent known as doxorubicin), has been shown to inhibit USP22 expression in a condition-specific manner ."
ZBED1 affects USP22
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1 |

No evidence text available
WD40 affects USP22
| 1
| 1

reach
"PALB2 WD40 Domain Directly Binds USP22 and stimulates its Catalytic Activity."
USP27X affects USP22
| 1
USP22 binds USP27X. 1 / 1
| 1

sparser
"All these results indicate that USP27X and the close homologue USP22 specifically interact and stabilize Snail1."
USP22 leads to the ubiquitination of transcriptional regulator. 1 / 1
| 1

reach
"Recent studies have demonstrated that USP22 can inhibit the transcription of the p21 gene by de-ubiquitinating the transcriptional regulator FBP1, leading to cell proliferation and tumorigenesis [XREF_BIBR]."
USP22 affects stemness features cells
| 1
USP22 activates stemness features cells. 1 / 1
| 1

eidos
"Thus , we speculated that the downregulation of USP22 by Gal-SLPs could block the glycolysis and further suppress stemness features in HCC cells ."
USP22 affects stem cell markers
| 1
USP22 activates stem cell markers. 1 / 1
| 1

eidos
"Downregulation of USP22 raised the sensitivity of PC cells to cisplatin , reduced the levels of stem cell markers , reduced the tumor sphere formation and migration , and promoted apoptosis ."
USP22 affects sorafenib chemosensitivity
| 1
USP22 inhibits sorafenib chemosensitivity. 1 / 1
| 1

eidos
"iv ) The downregulation of USP22 not only suppresses multidrug resistance-associated protein 1 ( MRP1 ) , enhances the intracellular accumulation of sorafenib , and finally inhibits cell proliferation and cancer angiogenesis , but also inhibits glycolysis in hepatocellular carcinoma ( HCC ) cells , enhancing sorafenib chemosensitivity and impairing cell metabolism ."
USP22 affects response DNA
| 1
USP22 inhibits response DNA. 1 / 1
| 1

eidos
"Additionally , upon genotoxic insult , both MAF and PCa models revealed that USP22 modulated the response to DNA damaging agents ."
USP22 affects protein p-PI3K
| 1
USP22 activates protein p-PI3K. 1 / 1
| 1

eidos
"The results showed that USP22 downregulation remarkably decreased the protein expression of p-PI3K and p-Akt without change in the total protein levels of PI3K and Akt ."
USP22 affects pro-inflammatory responses aeruginosa-induced keratitis
| 1
USP22 activates pro-inflammatory responses aeruginosa-induced keratitis. 1 / 1
| 1

eidos
"USP22 promotes pro-inflammatory responses in Pseudomonas aeruginosa-induced keratitis by targeting TRAF6 ."
USP22 affects picloram
| 1
| 1

eidos
"In our previous study , USP22 bound to SIRT1 and subsequently activated the AKT pathway , increasing the expression of MRP1 to induce 5-FU resistance in HCC cells [ 15 ] ."
USP22 affects pathways
| 1
USP22 activates pathways. 1 / 1
| 1

sparser
"Western blot analyses showed that the knockdown of SOS1 could also attenuate USP22-induced activation of the SOS1/RAS/ERK and SOS1/RAS/PI3K/AKT pathways in both SGC7901 cells and xenograft tumors (Fig.  xref b, c)."
| 1
| 1

reach
"USP22 promotes NSCs stemness maintenance and adult hippocampal neurogenesis, contributing to cognitive recovery following TBI."
USP22 affects miR-30-5p
| 1
USP22 binds miR-30-5p. 1 / 1
| 1

reach
"Furthermore, the binding of USP22 with the miR-30-5p family was confirmed by luciferase assay."
USP22 affects miR-144-3p
| 1
USP22 binds miR-144-3p. 1 / 1
| 1

reach
"The interaction between miR-144-3p and USP22 was validated by dual-luciferase reporter assay."
USP22 affects memory capacity
| 1
USP22 activates memory capacity. 1 / 1
| 1

eidos
"The Morris water maze ( MWM ) test was adopted to evaluate neurological function , which confirmed that USP22 could improve the learning and memory capacity that was already compromised following TBI ."
| 1

reach
"Furthermore, USP22 has been shown to promote antibody class switch recombination through non-homologous end joining (NHEJ) and also affected homologous recombination (HR) repair ."

eidos
"Significance : RNA demethylase ALKBH5 upregulates USP22 and RNF40 to inhibit histone H2A ubiquitination and induces expression of key replication and DNA repair-associated genes , driving osteosarcoma progression ."
USP22 affects growth metastasis cells
| 1
USP22 activates growth metastasis cells. 1 / 1
| 1

eidos
"The USP22 increases growth and metastasis of HCC cells via inducing Wnt / beta-catenin signaling ."
USP22 affects ganetespib
| 1
| 1

reach
"Depletion of USP22 in an in vivo model of colorectal cancer was shown to increase the therapeutic potentiation of ganetespib ."
USP22 affects function caused KCNQ1OT1
| 1
USP22 activates function caused KCNQ1OT1. 1 / 1
| 1

eidos
"The results show that overexpression of miR-30a-5p or inhibition of USP22 can reverse the inhibition of T-cell function caused by the high expression of KCNQ1OT1 ( p < 0.05 ) ( Figures 8G-I ) ."
USP22 affects foci
| 1
USP22 binds foci. 1 / 1
| 1

sparser
"Interestingly, immunostaining revealed that USP22 formed large nuclear foci that co-localized with PML bodies in telomerase-positive cells as well as in ALT cells, suggesting that USP22 is a constitutive component of PML bodies (Figure xref )."
| 1

eidos
"USP22 positively modulates ERalpha action via its deubiquitinase activity in breast cancer ."
USP22 affects deubiquitylation histones H2A
| 1
USP22 activates deubiquitylation histones H2A. 1 / 1
| 1

eidos
"USP22 was initially reported to promote deubiquitylation of histones H2A and H2B , leading to transcription activation ( 47 ) ."

reach
"This result suggests that USP22 is a potential diagnostic and a prognostic marker for GC patients.Previous studies show that USP22 promotes proliferation and survival of anaplastic thyroid [6], hepatic [13], colorectal [28], and bladder [29] cancer cells."
USP22 affects critical step
| 1
USP22 activates critical step. 1 / 1
| 1

eidos
"After viral infection , KPNA2 associates with IRF3 for nuclear import , and USP22 promotes this critical step by stabilizing KPNA2 ."
USP22 affects cl-caspase 3
| 1
USP22 inhibits cl-caspase 3. 1 / 1
| 1

reach
"In addition, USP22 knockdown combined with 5-Fu treatment further enhanced the down-regulation of Bcl-XL, Bcl-2 and up-regulated cl-caspase 3 and cleaved-caspase 9."
USP22 affects cerebral R-induced oxidative stress
| 1
USP22 activates cerebral R-induced oxidative stress. 1 / 1
| 1

eidos
"Accordingly , USP22 downregulation also attenuated cerebral I / R-induced oxidative stress , inflammation , and cell apoptosis in mice , thereby reducing nerve injury and neurological dysfunction [ 20 ] ."
USP22 affects beta-catenin nuclear localisation
| 1
USP22 activates beta-catenin nuclear localisation. 1 / 1
| 1

eidos
"Mechanistically , it has been reported that USP22 induces beta-catenin nuclear localisation and upregulates FoxM1 expression to promote G1 / S cell cycle transition and cell proliferation ( Ning et al ., 2014 ) ."
USP22 affects antiviral response cytoplasm
| 1
USP22 activates antiviral response cytoplasm. 1 / 1
| 1

eidos
"Just recently , Cai and colleagues reported that the ubiquitin specific peptidase 22 ( USP22 ) promotes the antiviral response from the cytoplasm by deubiquitinating importin KPNA2 [ 60 ] ."
USP22 affects ZBED1
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1 |

No evidence text available
USP22 affects XPC function
| 1
USP22 activates XPC function. 1 / 1
| 1

eidos
"Functional assessment revealed that USP22 significantly modulates XPC function through deubiquitylation , and that this pathway is critical for USP22-mediated DNA repair processes ."
USP22 affects WD40
| 1
| 1

reach
"PALB2 WD40 Domain Directly Binds USP22 and stimulates its Catalytic Activity."
USP22 affects UNC5CL
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1 |

No evidence text available
USP22 affects Tissues
| 1
USP22 activates Tissues. 1 / 1
| 1

eidos
"As a result , the data herein were the first to demonstrate USP22 independently promotes proliferation in normal tissue ."
USP22 affects TRIM69
| 1
USP22 activates TRIM69. 1 / 1
| 1

reach
"However, USP13, USP19, and USP22 inhibit virus-induced IFN production by removing K27-linked polyubiquitin chains from STING (40, 81) or TRIF (90)."
USP22 affects TRF1 deubiquitylation
| 1
USP22 activates TRF1 deubiquitylation. 1 / 1
| 1

eidos
"For example , USP22 promotes TRF1 deubiquitylation to enhance TRF1 protein stability and maintain telomere integrity ( 48 ) ."
USP22 affects TADA1
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1 |

No evidence text available
USP22 affects SPT3/TAF9/GCN5
| 1
USP22 binds SPT3/TAF9/GCN5. 1 / 1
| 1

reach
"Similarly, the ataxin-7 protein (ATXN7), which causes SCA7 when mutated, serves as a core component of epigenetic regulatory complexes -- the SPT3/TAF9/GCN5 and USP22 complexes, which have histone acetyltransferase and deubiquitination activity, respectively."
USP22 affects SOS1/RAS/ERK
| 1
USP22 activates SOS1/RAS/ERK. 1 / 1
| 1

reach
"Western blot analyses showed that the knockdown of SOS1 could also attenuate USP22-induced activation of the SOS1/RAS/ERK and SOS1/RAS/PI3K/AKT pathways in both SGC7901 cells and xenograft tumors (Fig. 6b, c)."
USP22 affects SND1
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1 |

No evidence text available
USP22 affects SIRT1 stability
| 1
USP22 activates SIRT1 stability. 1 / 1
| 1

eidos
"Teneligliptin treatment enhances SIRT1 stability and activity by USP22 , a ubiquitin specific peptidase ."
USP22 affects SIRT-1
| 1
USP22 binds SIRT-1. 1 / 1
| 1

trips
"USP22 interacts with and stabilizes Sirt1 by removing polyubiquitin chains conjugated onto Sirt1."
USP22 affects SCFD1
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1 |

No evidence text available
USP22 affects SAGA complex
| 1
USP22 activates SAGA complex. 1 / 1
| 1

reach
"Furthermore, endogenous USP22 contributes a deubiquitylating activity to the human SAGA complex, required for the function of transcription activators in eukaryotes XREF_BIBR."
USP22 affects RNPC3
| 1
| 1

sparser
"Looking more broadly across the genome, we found that sites that significantly gained H2BK120Ub in both Usp22KO and Usp22-RNP targeted Tregs were enriched for activating histone modifications (H3K4me3, H3K4me and H3K27ac) suggesting that changes occurred at gene regulatory elements, including at Treg-specific super enhancers ( xref , xref )."
USP22 affects RIPK3
| 1
| 1

sparser
"In addition, FLAG‐tagged, PAM‐mutated USP22 also interacts with endogenous RIPK3, independently of TBZ‐induced necroptosis (Fig  xref )."
USP22 affects PTGER4
| 1
USP22 increases the amount of PTGER4. 1 / 1
| 1

reach
"Silencing of USP22 or COX-2 significantly decreased the production of PGE2, whereas overexpression of COX-2 restored PGE2 levels downregulated by USP22, confirming that USP22 modulates COX-2 expressio[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 affects ODC1
| 1
USP22 increases the amount of ODC1. 1 / 1
| 1

reach
"Additionally, DHT stimulation in USP22 upregulated cells promoted a ~ 4-fold increase in ODC expression above DHT stimulated conditions (XREF_FIG), which was significantly sustained in LN-USP22 cells upon Casodex treatment (although compared to the AR targets examined in XREF_FIG, Casodex showed a relatively more pronounced inhibitory effect)."
USP22 affects Nodal
| 1
| 1

sparser
"The overexpression of USP22 was also significantly associated with poor tumor differentiation, distant tumor metastasis, positive nodal status and larger tumor size (>5 cm)."

reach
"In this study, we demonstrated that USP22 mediated protein stabilization of BMI1 promotes gastric CSC stemness maintenance and GC progression, thereby providing a rationale for USP22 targeting as a potential therapeutic approach against GC."
USP22 affects NPHP1
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1 |

No evidence text available

reach
"Here, we demonstrated that USP22 (ubiquitin specific peptidase 22) promotes NLRP3 degradation and inhibits NLRP3 inflammasome activation."
USP22 affects MRPL10
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1 |

No evidence text available
USP22 affects MIR101-1
| 1
| 1

reach
"USP22 restoration attenuated the inhibitory effects of miR-101 on PTC malignant traits in vitro."
USP22 affects MBD4
| 1
USP22 activates MBD4. 1 / 1
| 1

reach
"Instead, USP22 enhances MED1 functions for IL-2Rbeta and T-bet gene expression through deubiquitinating histone H2A but not H2B monoubiquitination."
USP22 affects KIF7
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1 |

No evidence text available
USP22 affects IL1B
| 1
USP22 activates IL1B. 1 / 1
| 1

reach
"Other inflammatory mediators secreted by PDA cells include granulocyte colony-stimulating factor (G-CSF) (41), IL-6 (42), IL-1α (43), IL-1β (44, 45), ubiquitin specific peptidase 22 (USP22) (46), C-X-C motif chemokine ligand 8 (CXCL8) (47), matrix metallopeptidase 9 (MMP-9) and indoleamine-2,3-dioxygenase (IDO) (48), which all contribute to the establishment of immunosuppressive TME in pancreatic cancer ( Figure 1 )."
USP22 affects IL-1α
| 1
USP22 activates IL-1α. 1 / 1
| 1

reach
"Other inflammatory mediators secreted by PDA cells include granulocyte colony-stimulating factor (G-CSF) (41), IL-6 (42), IL-1α (43), IL-1β (44, 45), ubiquitin specific peptidase 22 (USP22) (46), C-X-C motif chemokine ligand 8 (CXCL8) (47), matrix metallopeptidase 9 (MMP-9) and indoleamine-2,3-dioxygenase (IDO) (48), which all contribute to the establishment of immunosuppressive TME in pancreatic cancer ( Figure 1 )."
USP22 affects HATs
| 1
USP22 binds HATs. 1 / 1
| 1

reach
"The finding that two DUBs, 2A-DUB and USP22 associate with HATs suggests an important functional interplay between these classes of enzymes."

reach
"By impacting H2Bub1 levels, USP22 partakes in multiple pathways required for the maintenance of genome stability, and USP22 expression may be required to prevent aberrant events underlying genome instability."
USP22 affects GSC
| 1
USP22 activates GSC. 1 / 1
| 1

reach
"Likewise, knockdown of USP22 inhibited GSC stemness (XREF_FIG and XREF_SUPPLEMENTARY), and exogenous KDM1A rescued the effect of USP22 depletion on GSC stemness (XREF_FIG and XREF_SUPPLEMENTARY)."
USP22 affects GC cell EMT-induced metastasis
| 1
USP22 inhibits GC cell EMT-induced metastasis. 1 / 1
| 1

eidos
"Mechanistically , we found that miR-4490 directly targets USP22 , which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo ."
USP22 affects FUSE)-binding protein 1
| 1
USP22 activates FUSE)-binding protein 1. 1 / 1
| 1

reach
"Moreover, it has been shown that USP22 promotes cell growth by regulating the far upstream element (FUSE)-binding protein 1 (FBP1), a transcriptional regulator of p21 [XREF_BIBR]."
USP22 affects FLT3
| 1
USP22 binds SIRT1 and FLT3. 1 / 1
| 1

sparser
"We show that USP22 directly interacts with SIRT1 in FLT3-ITD AML cells in a FLT3-kinase-independent manner."
USP22 affects EMT process OS cells
| 1
USP22 activates EMT process OS cells. 1 / 1
| 1

eidos
"The results suggested that USP22 downregulation obviously suppressed the EMT process in OS cells ."
USP22 affects DUB module
| 1
USP22 binds DUB module. 1 / 1
| 1

reach
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) (Lan et al., 2015; Zhang et al., 2008b; Zhao et[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP22 affects CRPC-associated gene profile
| 1
USP22 increases the amount of CRPC-associated gene profile. 1 / 1
| 1

reach
"Most strikingly, USP22 deregulation induces androgen independent AR recruitment to target gene regulatory loci and subsequent expression of a CRPC associated gene profile, and supports cell growth and proliferation in the absence of androgens."
USP22 affects CREB3L1
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1 |

No evidence text available
USP22 affects CFHR1
| 1
USP22 activates CFHR1. 1 / 1
| 1

reach
"Immunoprecipitation of cross linked chromatin from HFL1 cells with an anti-Sp1 antibody followed by PCR amplification of the region (the sequence between-210 and +52) confirmed that the endogenous Sp1 protein does bind to this region of the USP22 promoter in HFL1 (XREF_FIG)."
USP22 affects CCND1
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USP22 activates CCND1. 1 / 1
| 1

eidos
"Moreover , experimentally increasing USP22 expression led to an increase in cyclin D1 and a more rapid progression through G1 , an effect which could be blocked by treating cells with a CDK4 / 6 inhibitor ."
USP22 affects BCL2L1
| 1
USP22 increases the amount of BCL2L1. 1 / 1
| 1

reach
"USP22 knockdown also decreased the expression of Bcl-XL and Bcl-2 and increased the expression of cleaved-caspase 3 and cleaved-caspase 9."
USP22 affects Aging
| 1
Modified USP22 inhibits Aging. 1 / 1
| 1

reach
"The overexpression of USP22 significantly enhanced cell proliferation potency and telomerase activity, elevated TERT expression level, inhibited p53 expression and cell aging, as well as decreased cell apoptosis or DNA damage."
USP22 affects ATXN7L3B
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No evidence text available
USP22 affects ATXN7L2
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1 |

No evidence text available
USP22 affects AKT/GSK-3/Cyclin
| 1
USP22 inhibits AKT/GSK-3/Cyclin. 1 / 1
| 1

reach
"USP22 knockdown was also found to modulate the AKT/GSK-3/Cyclin pathway, resulting in downregulation of p-AKT, p-GSK-3beta, and cyclinD1."
UNC5CL affects USP22
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1 |

No evidence text available
UMOD affects USP22
| 1
UMOD activates USP22. 1 / 1
| 1

reach
"Furthermore, the inhibition on the USP22 promoter activity by THP was not affected by overexpression of CREB-1 in HeLa cells."
UBP8 affects USP22
| 1
UBP8 deubiquitinates USP22. 1 / 1
| 1

reach
"It has been shown that Ubp8 deubiquitylates H2Bub on lysine 123 (H2BK123) and USP22 on H2BK120."
TADA1 affects USP22
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1 |

No evidence text available
SPT3/TAF9/GCN5 affects USP22
| 1
USP22 binds SPT3/TAF9/GCN5. 1 / 1
| 1

reach
"Similarly, the ataxin-7 protein (ATXN7), which causes SCA7 when mutated, serves as a core component of epigenetic regulatory complexes -- the SPT3/TAF9/GCN5 and USP22 complexes, which have histone acetyltransferase and deubiquitination activity, respectively."
SNHG16 knockdown affects USP22
| 1
SNHG16 knockdown increases the amount of USP22. 1 / 1
| 1

reach
"QRT-PCR results showed that the SNHG16 knockdown could inhibit the expression of USP22 in SW480 and SW620 cells, while the addition of miR-132-3p inhibitor could reverse this effect (XREF_FIG and B)."
SND1 affects USP22
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No evidence text available
SIRT1 affects FLT3
| 1
USP22 binds SIRT1 and FLT3. 1 / 1
| 1

sparser
"We show that USP22 directly interacts with SIRT1 in FLT3-ITD AML cells in a FLT3-kinase-independent manner."
SIRT-1 affects USP22
| 1
USP22 binds SIRT-1. 1 / 1
| 1

trips
"USP22 interacts with and stabilizes Sirt1 by removing polyubiquitin chains conjugated onto Sirt1."
SCFD1 affects USP22
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1 |

No evidence text available
RNPC3 affects USP22
| 1
| 1

sparser
"Looking more broadly across the genome, we found that sites that significantly gained H2BK120Ub in both Usp22KO and Usp22-RNP targeted Tregs were enriched for activating histone modifications (H3K4me3, H3K4me and H3K27ac) suggesting that changes occurred at gene regulatory elements, including at Treg-specific super enhancers ( xref , xref )."
RIPK3 affects USP22
| 1
| 1

sparser
"In addition, FLAG‐tagged, PAM‐mutated USP22 also interacts with endogenous RIPK3, independently of TBZ‐induced necroptosis (Fig  xref )."
Nodal affects USP22
| 1
| 1

sparser
"The overexpression of USP22 was also significantly associated with poor tumor differentiation, distant tumor metastasis, positive nodal status and larger tumor size (>5 cm)."
NPHP1 affects USP22
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1 |

No evidence text available
MiR-6825-5p affects USP22
| 1
MiR-6825-5p inhibits USP22. 1 / 1
| 1

reach
"MiR-6825-5p, miR-6845-5p, and miR-6886-3p were down-regulated by HULC, resulting in the elevation of Sirt1, USP22, and protective autophagy, thus attenuating the sensitivity of HCC cells to chemotherapeutic agents [82]."
MRPL10 affects USP22
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1 |

No evidence text available
MLN7243 affects USP22
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MLN7243 sumoylates USP22. 1 / 1
1 |

No evidence text available
MKI67 affects USP22
| 1
| 1

sparser
"Ki67 expression was associated with USP22 overexpression in cervical cancer, prostate cancer and oral squamous cell carcinoma [ xref , xref , xref ]."
KIF7 affects USP22
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1 |

No evidence text available
HIF1A affects USP22
| 1
HIF1A inhibits USP22. 1 / 1
| 1

reach
"In TP53 wild-type HCC cells, HIF1alpha induced TP53 mediated inhibition of HIF1alpha induced USP22 upregulation."
HATs affects USP22
| 1
USP22 binds HATs. 1 / 1
| 1

reach
"The finding that two DUBs, 2A-DUB and USP22 associate with HATs suggests an important functional interplay between these classes of enzymes."
FLT3 affects USP22
| 1
USP22 binds SIRT1 and FLT3. 1 / 1
| 1

sparser
"We show that USP22 directly interacts with SIRT1 in FLT3-ITD AML cells in a FLT3-kinase-independent manner."
EGFR affects USP22
| 1
EGFR activates USP22. 1 / 1
| 1

reach
"Additionally, a recent publication showed that USP22 modulated the activity of STAT3 indirectly by stabilizing EGFR, which indicated that USP22 and USP28 may have redundant effects in NSCLC."
| 1

sparser
"Although the interactions between MYC and some E3 ligases and deubiquitinases, such as CHIP, FBXL14, USP13 and USP22, are not identified yet in prostate cancer, the similar molecular mechanism enable them as probable targets for MYC degradation in prostate cancer."
1 |
Dietary Fats increases the amount of USP22. 1 / 1
1 |

No evidence text available
DYRK1A affects USP22
| 1
DYRK1A decreases the amount of USP22. 1 / 1
| 1

reach
"Inhibition of DYRK1A with EHT-5732 or lentivirus mediated knockdown of DYRK1A blocked the function of USP22 overexpression in the regulation of the proliferation and colony formation of PDAC cells."
DUB module affects USP22
| 1
USP22 binds DUB module. 1 / 1
| 1

reach
"The deubiquitinating enzyme USP22 (Ubp8 in yeast) closely associates with two adaptor proteins, ATXN7L3 and ENY2 (Sgf11 and Sus1 in yeast, respectively) (Lan et al., 2015; Zhang et al., 2008b; Zhao et[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Cyclin affects USP22
| 1
Cyclin activates USP22. 1 / 1
| 1

reach
"USP22 function reverses cyclin D1 ubiquitylation; overexpression of cyclin D1 can partially rescue cell cycle arrest in USP22 knockdown cells."
CREB3L1 affects USP22
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1 |

No evidence text available
CREB affects USP22
| 1
CREB activates USP22. 1 / 1
| 1

reach
"siRNA knockdown of CREB decreased USP22 transcriptional activation and endogenous expression, whereas CREB overexpression did not affect transcriptional levels."
CDH1 affects USP22
| 1
| 1

reach
"This interaction was specific because USP22 interaction with either CDH1 or FBW7 was not detected (XREF_FIG)."
ATXN7L3B affects USP22
1 |

No evidence text available
ATXN7L3 affects ATXN7
| 1
| 1

sparser
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC/STAGA ( Figure 1 D, lane 4)."
ATXN7L2 affects USP22
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1 |

No evidence text available
ATXN7 affects ATXN7L3, and USP22
| 1
| 1

sparser
"Western blot analysis of complexes obtained after an ATXN7 immunopurification showed that USP22 and ATXN7L3 associate with ATXN7 together with other components of TFTC/STAGA ( Figure 1 D, lane 4)."
APCCDC20 affects USP22
| 1
APCCDC20 inhibits USP22. 1 / 1
| 1

eidos
"Moreover , anaphase-promoting complex cell division cycle protein 20 ( APCCDC20 ) , an E3 ubiquitin ligase , promotes USP22 degradation in a cell cycle-dependent manner ( 61 ) ."
17alpha-ethynylestradiol increases the amount of USP22. 1 / 1
1 |

No evidence text available