IndraLab
Statements
USP22 affects cell population proliferation
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USP22 activates cell population proliferation.
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USP22 inhibits cell population proliferation.
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"Third, since USP7 has key roles in the p53 tumor suppressor pathway through stabilization of p53 via increasing MDM2 [6, 52], while USP22 is reported to antagonize p53 transcriptional activation by deubiquitinating Sirt1 to suppress [34], we further investigated p53p53 the effect of USP22 and USP7 inhibition on the p53 pathway."
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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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"Third, since USP7 has key roles in the p53 tumor suppressor pathway through stabilization of p53 via increasing MDM2 [6, 52], while USP22 is reported to antagonize p53 transcriptional activation by deubiquitinating Sirt1 to suppress [34], we further investigated p53p53 the effect of USP22 and USP7 inhibition on the p53 pathway."
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"USP22 can reduce Ku70 acetylation by stabilizing SIRT1 expression, thereby inhibiting Bax-mediated apoptosis and promoting cisplatin resistance.ALDH1A3, a major ALDH isoenzyme, is important for the stem cell signature of lung cancer and is associated with enhanced cisplatin resistance in lung adenocarcinoma."
USP22 affects apoptotic process
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USP22 inhibits apoptotic process.
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USP22 activates apoptotic process.
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USP22 affects Neoplasm Invasiveness
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USP22 activates Neoplasm Invasiveness.
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USP22 activates Neoplasm Invasiveness. 10 / 52
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USP22 activates Neoplasm Invasiveness. 9 / 9
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USP22 inhibits Neoplasm Invasiveness.
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USP22 inhibits Neoplasm Invasiveness. 10 / 18
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USP22 inhibits Neoplasm Invasiveness. 8 / 8
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"The decreased expression of the deubiquitinase USP22 in pancreatic cancer cells promoted the infiltration of natural killer and T cells, thereby enhancing the anti-tumor immune response of the TME.91 Ubiquitination modification also regulates T cells to promote the differentiation of other cells."
sparser
"The loss of USP22 causes PD-L1 to be degraded at the post-translational level, which has been shown to reduce carcinogenesis and increase T cell-mediated cell death. xref PD-L1 targeted immunotherapy and CDDP-based chemotherapy were both shown to benefit from USP22 reduction in another research, highlighting the complex and important functions of the USP22-PD-L1 axis in cancer treatment. xref According to a recent research, the tumor-promoting long noncoding RNA (lncRNA) KCNQ1OT1 controls the ubiquitination of PD-L1 and decreases the response of CD8 + T cells via the miR-30a-5p/USP22 pathway."
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"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]."
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"The loss of USP22 causes PD-L1 to be degraded at the post-translational level, which has been shown to reduce carcinogenesis and increase T cell-mediated cell death.101 PD-L1 targeted immunotherapy and CDDP-based chemotherapy were both shown to benefit from USP22 reduction in another research, highlighting the complex and important functions of the USP22-PD-L1 axis in cancer treatment."
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"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."
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"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)."
USP22 affects Neoplasm Metastasis
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USP22 activates Neoplasm Metastasis.
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USP22 inhibits Neoplasm Metastasis.
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"61 In contrast, c-Myc promotes apoptosis and accelerates cell turnover during cellular carcinogenesis, thereby promoting the progression of cells toward increasingly malignant phenotypes.73 Therefore, it is hypothesized that USP22 promotes cancer progression in BC cells by stabilizing c-Myc to promote apoptosis."
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"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."
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"It has been established that USP22 is required for c-MYC transcriptional activity, through a direct mechanism where USP22 deubiquitylates c-MYC, causing its stabilization or activation, or indirectly through the recruitment of other transcriptional machinery, or by the removal of ubiquitin from histones at c-MYC target genes."
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"The loss of USP22 can reduce the transcription of Myc and p53 by removing Ub from H2B.27 USP3 and USP21 also have functions in chromatin modification, leading to aberrant gene transcription.28 Loss of USP3 results in defects of the cell cycle, while USP21 can promote regenerative functions in hepatocytes."
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."
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"The loss of USP22 can reduce the transcription of Myc and p53 by removing Ub from H2B.27 USP3 and USP21 also have functions in chromatin modification, leading to aberrant gene transcription.28 Loss of USP3 results in defects of the cell cycle, while USP21 can promote regenerative functions in hepatocytes."
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"In addition, our immunofluorescence analysis showed that Importin-7 binds to AR or USP22 in both the nucleus and cytoplasm (Fig. 4C–E), suggesting that Importin-7 may regulate the nuclear translocation of AR and USP22.Next, we conducted a more in-depth study of the Importin-7–AR–USP22 complex by the treatment of AR inhibitor (enzalutamide) or AR ligands, including DHT and synthetic androgen R1881."
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"Here, to further investigate whether the arrest of the nuclear translocation of AR–USP22 complex triggered by the knockdown of Importin-7 could enhance the sensitivity of BC to enzalutamide.We first confirmed that the knockdown of Importin-7 could enhance the growth inhibition of cancer cells by enzalutamide using CCK8 assay (Fig. 6A, B) and EdU staining assay (Fig. 6C, D)."
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"Interestingly, we found that USP22, one of the maintainers of AR [22–24], whose nuclear translocation is also regulated by Importin-7, although knockdown of Importin-7 may not affect the formation of the AR–USP22 complex.In addition, we also observed that AR expression levels were upregulated after DHT and R1881 stimulation, and Importin-7-bound AR was also up-regulated to an almost equal extent, indicating that the level of AR carried by Importin-7 was not saturated."
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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."
USP22 is modified
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USP22 is phosphorylated.
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USP22 is ubiquitinated.
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USP22 is acetylated.
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"In an attempt to separate the HAT activity from the DUB interaction domain to assess the contribution of both acetylation and deubiquitylation of PCAF and USP22, we generated an enzymatically dead PCAF by installing two mutations in the core HAT domain (PCAF-YFAA [Y616A/F617A] mutant) (; xref )."
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."
USP22 affects cell cycle
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USP22 activates cell cycle.
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USP22 inhibits cell cycle.
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USP22 activates epithelial to mesenchymal transition.
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USP22 activates epithelial to mesenchymal transition. 10 / 38
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"In the context of EMT induction, miR-30e is an important EMT inhibitor that works by targeting ITGB1, TUSC3, USP22, and SOX9 mRNAs, which reportedly induce EMT by activating transcription factors including SNAIL, SLUG, TWIST, and ZEB1/2 [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
USP22 inhibits epithelial to mesenchymal transition.
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USP22 inhibits epithelial to mesenchymal transition. 6 / 6
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"In this study, we found that quercetin significantly inhibited the expression of USP22 and Snail1 in high glucose (HG)-induced renal tubular epithelial cells (TECs), and reversed the expression of EMT-related proteins and inhibited the overproduction of fibronectin (FN) and Collage Type IV (Collagen IV) induced by high glucose."
sparser
"At the same time, the loss of OTUD7B promotes the binding of LSD1 to P62, a polyubiquitin chain binding protein, leading to LSD1 proteasomal degradation. xref USP28 (ubiquitin-specific protease 28) catalyzes deubiquitination of LSD1 through the N-terminal region of USP28 and the AOL domain of LSD1 to stabilize LSD1 protein, which enables direct regulation of the expression of differentiation genes, indirectly regulating the expression of the pluripotency activators. xref In glioma, a lack of methionine inhibits the growth of cancer cells and enhances the binding of LSD1 to E3 ubiquitin ligase CBL (casitas B-lineage lymphoma), and increased ubiquitination of LSD1 enhances expression of CXCL8 (CXC motif chemokine ligand 8) and methylated histone H3, which in turn affects the metabolism of the glycerophospholipid. xref USP7 (ubiquitin-specific protease 7) is able to interact with LSD1, exercising deubiquitination functions and enhancing the inhibitory effect of LSD1 on p53 (tumor protein p53). xref , xref , xref Phosphorylation of LSD1 catalyzed by GSK3β promotes the binding of LSD1 to USP22 (ubiquitin specific protease 22), and deubiquitination of LSD1 promotes tumor formation. xref , xref USP38 (ubiquitin-specific protease 38) interacts with LSD1 at amino acid 454 to stabilize protein level."
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"40 In glioma, a lack of methionine inhibits the growth of cancer cells and enhances the binding of LSD1 to E3 ubiquitin ligase CBL (casitas B-lineage lymphoma), and increased ubiquitination of LSD1 enhances expression of CXCL8 (CXC motif chemokine ligand 8) and methylated histone H3, which in turn affects the metabolism of the glycerophospholipid.41 USP7 (ubiquitin-specific protease 7) is able to interact with LSD1, exercising deubiquitination functions and enhancing the inhibitory effect of LSD1 on p53 (tumor protein p53).42, 43, 44 Phosphorylation of LSD1 catalyzed by GSK3β promotes the binding of LSD1 to USP22 (ubiquitin specific protease 22), and deubiquitination of LSD1 promotes tumor formation.29 45 USP38 (ubiquitin-specific protease 38) interacts with LSD1 at amino acid 454 to stabilize protein level."
USP22 affects cell growth
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USP22 activates cell growth.
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USP22 inhibits cell growth.
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"SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability, but inhibition of SIRT1 expression or activity reduced the growth of FLT3-ITD AML LSCs and significantly enhanced TKI-mediated killing of the cells."
sparser
"The loss of USP22 causes PD-L1 to be degraded at the post-translational level, which has been shown to reduce carcinogenesis and increase T cell-mediated cell death. xref PD-L1 targeted immunotherapy and CDDP-based chemotherapy were both shown to benefit from USP22 reduction in another research, highlighting the complex and important functions of the USP22-PD-L1 axis in cancer treatment. xref According to a recent research, the tumor-promoting long noncoding RNA (lncRNA) KCNQ1OT1 controls the ubiquitination of PD-L1 and decreases the response of CD8 + T cells via the miR-30a-5p/USP22 pathway."
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"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)."
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 )."
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"Our data indicate physical interaction between USP22 and FoxM1 is required for USP22-mediated suppression of FoxM1 ubiquitination, because mutation of cystines 61 and 63, which disrupts the zinc finger structure and its interaction with FoxM1 ( xref ), totally abolished USP22 activity in suppressing FoxM1 ubiquitination ( xref )."
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"Our data indicate physical interaction between USP22 and FoxM1 is required for USP22-mediated suppression of FoxM1 ubiquitination, because mutation of cystines 61 and 63, which disrupts the zinc finger structure and its interaction with FoxM1 (Fig. 3I), totally abolished USP22 activity in suppressing FoxM1 ubiquitination (Fig. 3G)."
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"By contrast, treatment with NH Cl, an inhibitor of endosome-lysosome degradation pathway, fails to protect FoxM1 from degradation (Figure s3A), suggesting that USP22 promotes FoxM1 level through inhibiting its proteasomal degradation.As a deubiquitinase, USP22 exerts its biological function largely through protecting its downstream substrates from ubiquitination-mediated degradation ."
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"By contrast, treatment with NH Cl, an inhibitor of endosome-lysosome degradation pathway, fails to protect FoxM1 from degradation (Figure S3A), suggesting that USP22 promotes FoxM1 expression by inhibiting its proteasomal degradation.As a deubiquitinase, USP22 exerts its biological function largely through protecting its downstream substrates from ubiquitination-mediated degradation.27 Accordingly, we speculated that USP22 could be a deubiquitinase of FoxM1."
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"Our data indicate physical interaction between USP22 and FoxM1 is required for USP22-mediated suppression of FoxM1 ubiquitination, because mutation of cystines 61 and 63, which disrupts the zinc finger structure and its interaction with FoxM1 (Fig. 3I), totally abolished USP22 activity in suppressing FoxM1 ubiquitination (Fig. 3G)."
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"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)."
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 )."
USP22 affects Histone_H2B
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USP22 deubiquitinates Histone_H2B.
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USP22 deubiquitinates Histone_H2B. 10 / 27
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"Apart from deubiquitinating histones H2A and H2B, USP22 also modulates transcription through stabilization of the p53-antagonizing deacetylase sirtuin-1 (SIRT1) to suppress p53-controlled transcription and to abrogate pre-mature senescence in pluripotent progenitor cells during embryonic development [5]."
USP22 ubiquitinates Histone_H2B.
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"Of note, mass spectrometry (MS) analysis also detected 10 AKT phosphorylated peptides in the anti-USP22 immunoprecipitants ( xref ), confirming our initial discovery of AKT-USP22 interaction and suggesting that USP22 interacts with the phosphorylated AKT upon EPI stimulation in breast cancer cells."
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"Reduction of ZEB1 caused by knockdown of USP22 was also prevented by MG132, on the other hand, USP22 depletion accelerated ZEB1 degradation with the treatment of cycloheximide (CHX), which is protein synthesis inhibitor, in HCC-derived cells (Fig. 4D–F and Supplementary Fig. S5A)."
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"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]."
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
"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."
USP22 affects H2Bub1
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USP22 activates H2Bub1.
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USP22 deubiquitinates H2Bub1.
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USP22 inhibits H2Bub1.
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USP22 decreases the amount of H2Bub1.
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USP22 increases the amount of H2Bub1.
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"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."
USP22 affects Carcinogenesis
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USP22 activates Carcinogenesis.
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USP22 inhibits Carcinogenesis.
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"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)."
USP22 affects Stomach Neoplasms
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USP22 activates Stomach Neoplasms.
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USP22 inhibits Stomach Neoplasms.
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"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]."
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
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"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."
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USP22 affects ferroptosis
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USP22 inhibits ferroptosis.
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USP22 inhibits ferroptosis. 10 / 17
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"Additionally, A549 and H1975 LUAD cells with USP22 silencing exhibited a higher expression of ACSL4 and lower levels of SLC7A11 and GPX4 than sh‐Ctrl controls; however, these changes could be markedly reversed by COL17A1 reexpression (Figure 6J,K), indicating that USP22 silencing induces cell ferroptosis via COL17A1 downregulation."
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"Finally, in vivo study proved that miR-144-3p antagomir could restore the impaired function of pancreatic β-cells by suppressing ferroptosis to exert anti-hyperglycemic effect on T2DM mice.In short, the abnormal up-regulation of miR-144-3p clearly suppressed the expression of USP22 mRNA and inhibited its downstream effects on the ferroptosis pathway to cause the dysfunction of pancreatic β cells (Fig. 6), thereby promoting the progression of T2DM."
USP22 activates ferroptosis.
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USP22 activates ferroptosis. 3 / 3
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"USP22 promotes the proliferation of hepatocellular carcinoma cells by stabilising CDK11B and enhances resistance to Sorafenib by inhibiting ferroptosis through the USP22/H2BK120ub/TFRC axis.So far, more than 40 USPs have been directly or indirectly associated with relevant cancer processes."
sparser
"At the same time, the loss of OTUD7B promotes the binding of LSD1 to P62, a polyubiquitin chain binding protein, leading to LSD1 proteasomal degradation. xref USP28 (ubiquitin-specific protease 28) catalyzes deubiquitination of LSD1 through the N-terminal region of USP28 and the AOL domain of LSD1 to stabilize LSD1 protein, which enables direct regulation of the expression of differentiation genes, indirectly regulating the expression of the pluripotency activators. xref In glioma, a lack of methionine inhibits the growth of cancer cells and enhances the binding of LSD1 to E3 ubiquitin ligase CBL (casitas B-lineage lymphoma), and increased ubiquitination of LSD1 enhances expression of CXCL8 (CXC motif chemokine ligand 8) and methylated histone H3, which in turn affects the metabolism of the glycerophospholipid. xref USP7 (ubiquitin-specific protease 7) is able to interact with LSD1, exercising deubiquitination functions and enhancing the inhibitory effect of LSD1 on p53 (tumor protein p53). xref , xref , xref Phosphorylation of LSD1 catalyzed by GSK3β promotes the binding of LSD1 to USP22 (ubiquitin specific protease 22), and deubiquitination of LSD1 promotes tumor formation. xref , xref USP38 (ubiquitin-specific protease 38) interacts with LSD1 at amino acid 454 to stabilize protein level."
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"40 In glioma, a lack of methionine inhibits the growth of cancer cells and enhances the binding of LSD1 to E3 ubiquitin ligase CBL (casitas B-lineage lymphoma), and increased ubiquitination of LSD1 enhances expression of CXCL8 (CXC motif chemokine ligand 8) and methylated histone H3, which in turn affects the metabolism of the glycerophospholipid.41 USP7 (ubiquitin-specific protease 7) is able to interact with LSD1, exercising deubiquitination functions and enhancing the inhibitory effect of LSD1 on p53 (tumor protein p53).42, 43, 44 Phosphorylation of LSD1 catalyzed by GSK3β promotes the binding of LSD1 to USP22 (ubiquitin specific protease 22), and deubiquitination of LSD1 promotes tumor formation.29 45 USP38 (ubiquitin-specific protease 38) interacts with LSD1 at amino acid 454 to stabilize protein level."
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"14 However, the Lnc-ZFAS1-mediated mechanism in osteosarcoma still remains insufficient.Recently, the dysregulation of miRNAs has been verified closely correlated with tumors growth and metastasis,15 and accumulating studies have proved the crucial role of miRNAs in osteosarcoma, like miR-411-5p,2 miR-53916 and miR-4660.17 Liu W et al. suggested miR-140 could weak the protein stabilization of LSD1 mediated by targeting USP22 and facilitate the expression of p21 to block osteosarcoma progression.18 Interestingly, Wang J et al. have reported the suppressive influence of miR-520b on growth and metastasis in osteosarcoma."
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"Apart from deubiquitinating histones H2A and H2B, USP22 also modulates transcription through stabilization of the p53-antagonizing deacetylase sirtuin-1 (SIRT1) to suppress p53-controlled transcription and to abrogate pre-mature senescence in pluripotent progenitor cells during embryonic development [5]."
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"Our studies indicate that USP22 acting as a histone deubiquitinase participates in deubiquitination of histone H2Bub on the promoter of VEGFA, co-activating ZEB1-mediated VEGFA transcription.It has been reported that ubiquitination modification on ZEB1 involved in maintenance of ZEB1 stability plays important roles in tumor progression."
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
"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."
USP22 affects inflammatory response
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USP22 inhibits inflammatory response.
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USP22 inhibits inflammatory response. 9 / 9
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"Thus, we infer that the possible mechanism is that in the early stage of inflammation, USP22 reduces the level of cellular inflammation through compensatory cytoplasmic translocation, and when the inflammatory stimulus is prolonged, USP22 is in a state of loss of compensation, its expression decreases markedly, and the cell undergoes a strong inflammation."
USP22 activates inflammatory response.
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USP22 affects immune response
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USP22 inhibits immune response.
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USP22 activates immune response.
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"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
"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)."
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
"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
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)."
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 )."
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"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]."
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"Based on our results, the ferroptosis inhibitor liproxstatin‐1 partially rescued the inhibitory effect of topotecan on metastasis, indicating that pharmacological inhibition of USP22 could partially suppress melanoma metastasis by enhancing ferroptosis sensitivities.Previously, Yi et al.
53
revealed that activating mutations in PI3K or loss of PTEN mediate the ferroptosis resistance of cancer cells."
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"Ablation of USP22 in immunosuppressive regulatory T cells leads to reduced tumor burden in several cancers.56 Importantly, USP22 promotes tumorigenesis and progression in HCC, by promoting stemness.53,57As hepatic expression of CXCL13 and SCF genes strongly correlated with tumor burden, we tested their potential as circulating HCC biomarkers."
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"Recent studies demonstrate that USP22 is a promising target for cancer immunotherapy, since USP22 positively regulates FOXP3 activity in mouse Treg cells that suppress antitumor immune responses, and Treg-specific USP22-knockout (USP22-Ko) suppressed in vivo Treg function to improve antitumor immunity [31]."
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"T cells from the dKO mice displayed a GSEA and bulk gene expression signature that merged the changes found in each of the single KO mice, suggesting that the loss of both Usp22 and Usp21 synergizes to diminish T cell function (Fig. 4G) in both Foxp3-depedent and Foxp3-independent manner.As we demonstrated that both Usp22 and Usp21 are regulated by metabolic alterations in the TME, it was particularly interesting to identify disruption of multiple metabolic pathways in each of the KO groups."
sparser
"Of note, mass spectrometry (MS) analysis also detected 10 AKT phosphorylated peptides in the anti-USP22 immunoprecipitants ( xref ), confirming our initial discovery of AKT-USP22 interaction and suggesting that USP22 interacts with the phosphorylated AKT upon EPI stimulation in breast cancer cells."
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"In addition to USP22, many other downstream factors, such as breast cancer resistance protein of AKT, are involved in drug resistance of breast cancers (56); therefore, future works are needed to dissect each substrate of phosphatidylinositol 3-kinase–AKT pathways in breast cancer tumorigenesis.One unexpected observation is the EPI-induced posttranscriptional stabilization of USP22, the cancer stem cell gene with increased expression in breast cancer stem cells (18)."
USP22 affects cell migration
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"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."
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"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."
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"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]."
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USP22 affects apoptotic cell clearance
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USP22 activates apoptotic cell clearance. 10 / 14
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"In this study, we likewise found that silencing USP22 promotes the uptake of oxidized lipoproteins, which may inhibit macrophage efferocytosis.Interestingly, in this study, we found that USP22 promoted the expression of efferocytosis-associated receptors as well as bridging molecules and that this regulation is dependent on the activation of PPARγ."
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"Our results showed that the PPARγ agonist rosiglitazone reversed the decrease in macrophage efferocytosis caused by USP22 silencing (Fig. 5H–J, Supplementary Fig. S5A, B. Furthermore, for THP-1-derived macrophages under inflammatory conditions, USP22 overexpression also promoted efferocytosis."
sparser
"For instance, the USP22-PPARγ axis plays a significant role in modulating both adipogenesis and inflammation, whereas disorders in bile acid metabolism and alterations in gut microbiota exhibit bidirectional regulation. xref In light of these mechanisms, preclinical studies have led to the development of small-molecule inhibitors that target USP22 and FXR."
sparser
"Interestingly, we found that USP22 strongly bound to the PPARγ DBD domain (Fig. xref ) as well as pVHL and CUL4B proteins in the HCC cells (Supplementary Fig. xref ), and the interaction between PPARγ and USP22 significantly decreased the pVHL and CRL4B AhR involved ubiquitination (Fig. xref ), indicating that USP22 regulates deubiquitination of PPARγ through other lysine sites."
USP22 affects Osteosarcoma
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USP22 activates Osteosarcoma.
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USP22 activates Osteosarcoma. 9 / 10
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"In addition, deficiency of ALKBH5‐mediated m6A modification in osteosarcoma causes an increase expression of histone deubiquitinase USP22 and ubiquitin ligase RNF40, which inhibits histone H2AK199 monoubiquitination, induces the expression of genes related to DNA repair, and promotes the progression of osteosarcoma."
USP22 inhibits Osteosarcoma.
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USP22 inhibits Osteosarcoma. 4 / 4
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"In addition, deficiency of ALKBH5‐mediated m6A modification in osteosarcoma causes an increase expression of histone deubiquitinase USP22 and ubiquitin ligase RNF40, which inhibits histone H2AK199 monoubiquitination, induces the expression of genes related to DNA repair, and promotes the progression of osteosarcoma."
sparser
"EPI stimulation, which induced USP22 protein expression and promoted USP22-FOXO1 interaction, markedly inhibited FOXO1 polyubiquitination in USP22 WT cancer cells, and targeted USP22 deletion resulted in a significant increase in FOXO1 ubiquitination and reduced FOXO1 protein expression even with EPI stimulation ( xref )."
USP22 affects Carcinoma, Hepatocellular
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USP22 activates Carcinoma, Hepatocellular. 10 / 14
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"USP22 promotes the proliferation of hepatocellular carcinoma cells by stabilising CDK11B and enhances resistance to Sorafenib by inhibiting ferroptosis through the USP22/H2BK120ub/TFRC axis.So far, more than 40 USPs have been directly or indirectly associated with relevant cancer processes."
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"Why USP22 has a preference for H2BK120ub as its substrate under Sorafenib treatment is worth further research.In summary, our study demonstrated that USP22 promotes the growth of hepatocellular carcinoma and resistance to Sorafenib‐induced ferroptosis by removing ubiquitin moieties from non‐histone protein CDK11B and histone H2B."
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"19
However, there has been a lack of thorough investigation into the role of USP22 in hepatocellular carcinoma development and Sorafenib resistance.In this study, we demonstrate that USP22 promotes the proliferation of hepatocellular carcinoma cells by stabilising cyclin‐dependent kinase 11B (CDK11B)."
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"These results indicate that EPI induces USP22 phosphorylation both in vitro and in tumor tissues in an AKT-dependent manner.We then analyzed the phospho-USP22 (p-USP22) levels by IHC staining using specific antibodies to one of the USP22 phosphorylation sites, T147, that is catalyzed by AKT (Fig. 6, A and B)."
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"EPI stimulation, which induced USP22 protein expression and promoted USP22-FOXO1 interaction, markedly inhibited FOXO1 polyubiquitination in USP22 WT cancer cells, and targeted USP22 deletion resulted in a significant increase in FOXO1 ubiquitination and reduced FOXO1 protein expression even with EPI stimulation (Fig. 4P)."
sparser
"Our data indicate physical interaction between USP22 and FoxM1 is required for USP22-mediated suppression of FoxM1 ubiquitination, because mutation of cystines 61 and 63, which disrupts the zinc finger structure and its interaction with FoxM1 ( xref ), totally abolished USP22 activity in suppressing FoxM1 ubiquitination ( xref )."
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"Our data indicate physical interaction between USP22 and FoxM1 is required for USP22-mediated suppression of FoxM1 ubiquitination, because mutation of cystines 61 and 63, which disrupts the zinc finger structure and its interaction with FoxM1 (Fig. 3I), totally abolished USP22 activity in suppressing FoxM1 ubiquitination (Fig. 3G)."
USP22 affects cell differentiation
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USP22 activates cell differentiation.
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USP22 inhibits cell differentiation.
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"In addition, considering that the ubiquitination of β-catenin could be reduced by the inhibition of demethylase activity of KDM2A and the methylation of β-catenin increased by USP22, we speculate that there may be a competition between the methylation and ubiquitination modification of β-catenin."
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USP22 activates diphenylmethane-4,4'-diisocyanate.
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USP22 increases the amount of diphenylmethane-4,4'-diisocyanate.
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"In addition, our immunofluorescence analysis showed that Importin-7 binds to AR or USP22 in both the nucleus and cytoplasm (Fig. 4C–E), suggesting that Importin-7 may regulate the nuclear translocation of AR and USP22.Next, we conducted a more in-depth study of the Importin-7–AR–USP22 complex by the treatment of AR inhibitor (enzalutamide) or AR ligands, including DHT and synthetic androgen R1881."
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"Here, to further investigate whether the arrest of the nuclear translocation of AR–USP22 complex triggered by the knockdown of Importin-7 could enhance the sensitivity of BC to enzalutamide.We first confirmed that the knockdown of Importin-7 could enhance the growth inhibition of cancer cells by enzalutamide using CCK8 assay (Fig. 6A, B) and EdU staining assay (Fig. 6C, D)."
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"Interestingly, we found that USP22, one of the maintainers of AR [22–24], whose nuclear translocation is also regulated by Importin-7, although knockdown of Importin-7 may not affect the formation of the AR–USP22 complex.In addition, we also observed that AR expression levels were upregulated after DHT and R1881 stimulation, and Importin-7-bound AR was also up-regulated to an almost equal extent, indicating that the level of AR carried by Importin-7 was not saturated."
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"In addition, deficiency of ALKBH5‐mediated m6A modification in osteosarcoma causes an increase expression of histone deubiquitinase USP22 and ubiquitin ligase RNF40, which inhibits histone H2AK199 monoubiquitination, induces the expression of genes related to DNA repair, and promotes the progression of osteosarcoma."
USP22 affects DNA-templated transcription
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USP22 activates DNA-templated transcription.
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USP22 activates DNA-templated transcription. 9 / 9
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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."
USP22 inhibits DNA-templated transcription.
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"19
However, there has been a lack of thorough investigation into the role of USP22 in hepatocellular carcinoma development and Sorafenib resistance.In this study, we demonstrate that USP22 promotes the proliferation of hepatocellular carcinoma cells by stabilising cyclin‐dependent kinase 11B (CDK11B)."
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"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."
sparser
"For instance, the USP22-PPARγ axis plays a significant role in modulating both adipogenesis and inflammation, whereas disorders in bile acid metabolism and alterations in gut microbiota exhibit bidirectional regulation. xref In light of these mechanisms, preclinical studies have led to the development of small-molecule inhibitors that target USP22 and FXR."
sparser
"Interestingly, we found that USP22 strongly bound to the PPARγ DBD domain (Fig. xref ) as well as pVHL and CUL4B proteins in the HCC cells (Supplementary Fig. xref ), and the interaction between PPARγ and USP22 significantly decreased the pVHL and CRL4B AhR involved ubiquitination (Fig. xref ), indicating that USP22 regulates deubiquitination of PPARγ through other lysine sites."
USP22 affects signal transduction
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USP22 activates signal transduction.
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USP22 activates signal transduction. 7 / 7
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"Collectively, our findings indicate that miR-200b-5p-mediated inhibition of USP22 attenuates cell proliferation by targeting the NF-κB signaling pathway in GC, suggesting that miR-200b-5p and USP22 could serve as potential diagnostic or therapeutic targets for gastric cancer and other related human diseases."
USP22 inhibits signal transduction.
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USP22 affects regulation of cell cycle
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USP22 activates regulation of cell cycle.
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USP22 activates regulation of cell cycle. 6 / 6
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"Mechanistic analysis has further demonstrated that knockdown of ALKBH5 induces cell cycle arrest by destabilizing ubiquitin-specific peptidase (USP22) and ubiquitin ligase ring finger protein 40 (RNF40), resulting in the upregulation of p27Kip1 and Wee1, which are cyclin-dependent kinase inhibitory proteins, and downregulation of cell cycle and DNA damage and repair-related genes in osteosarcoma cells."
USP22 inhibits regulation of cell cycle.
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USP22 affects glycolytic process
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USP22 activates glycolytic process. 10 / 11
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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 ."
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"In addition to integrin b1, USP22 deletion led to a modest but statistically significant reduction in several additional integrin family members including integrin a1–6 and integrin b2–3, b5–7, but not b4, b8 and a7–8 expression (Figure s2B), In contrast, integrin b6 expression is slightly increased in USP22-null breast cancer cells (Figure s2B)."
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"Therefore, USP22 appears to regulate the expression of multiple integrin family members with b1 as the dominant one.We then focused on studying the functional consequences of USP22-mediated integrin b1 upregulation and assessed whether USP22 maintains breast CSC self-renewal and promotes breast cancer metastasis through integrin b1 upregulation by ectopic reconstitution of ITGB1 in USP22 knockout cells (Figure s2C-E)."
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"We then focused on studying the functional consequences of USP22-mediated integrin β1 upregulation and assessed whether USP22 maintains BCSCs self-renewal and promotes breast cancer metastasis through integrin β1 upregulation by ectopic reconstitution of ITGB1 in USP22 knockout cells (Figures S2C–S2E)."
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
"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."
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"To demonstrate the upregulation of USP22 by USP7 knockdown is associated with desuppression of SP1 transcriptional activity, USP7 was knocked down, 24 h later, control plasmid and SP1 plasmids were individually introduced to overexpress SP1 in H1299 cells, additional 48 h later, proteins were extracted, Western blot analysis showed that reintroduction of SP1 significantly attenuated the upregulation of USP22 by USP7 knockdown (Fig. 2D)."
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
"About the possible relationship among BMI1 , EZH2 , and USP22 , it has been reported that USP22 increases BMI1 : in gastric cancer, USP22 inactivation decreases the neoplasm growth, while high levels of BMI1 accelerate the cell cycle via INK4a/ARF and AKT. xref Moreover, a reciprocal interaction between EZH2 and USP22 has been described in the sepsis‐induced myocardial dysfunction model: in this case, EZH2 represses USP22 through the H3K27me3 modification. xref In acute myeloid leukemia, the activation of BAX and the inhibition of BCL2 lead to a reduced expression of BMI1 and EZH2 . xref Finally, both BMI1 and EZH2 seem to be targets for the same miRNA, the miR200 that is a key regulator of the epithelial‐mesenchymal transition; indeed, a reduced expression of these genes reduces the migration capacity of colon cancer cells. xref "
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"In the study, we found that USP7 inhibition by three inhibitors: HBX4418 [45], P5091 [41], and FT671 [12] dramatically upregulates USP22 in cancer cells through transcriptional mechanisms, and given the critical role of USP22 in carcinogenesis and anticancer response, we propose that the upregulated USP22 may represent a critical side-effects of USP7 inhibition.We further examined the expression and activation of downstream signaling of USP22 pathway by USP7 inhibition and found that this feedback upregulation has a significant impact on USP22 pathway and USP22-related oncogenes."
USP22 affects Cell Survival
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USP22 activates Cell Survival.
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USP22 inhibits Cell Survival.
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HULC affects USP22
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HULC activates USP22.
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"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."
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"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."
HULC inhibits USP22.
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HULC increases the amount of USP22.
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"The results showed that, overexpression of USP22 significantly promoted the growth of HCC, and knockdown of ZEB1 inhibited the effect of USP22 on tumor growth (Fig. 6G–J), suggesting that ZEB1 was involved in the development of HCC, and the promotion of HCC growth by USP22 was partially related to ZEB1.In addition, the results from immunohistochemistry showed that USP22 depletion decreased USP22, ZEB1, or VEGFA expression in xenograft tumors."
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"Differential regulation of gene expression, as well as loss of USP22 expression, was also demonstrated by independent qRT-PCR of the USP22-dependent upregulated genes TGFB1, SLFN5, TGM2, and DDX60, as well as downregulation of USP22, CXCR4, and AK4 (Fig. 1C), confirming the quality of the microarray."
sparser
"USP22 protein contains an N‐terminal zinc‐finger (ZnF) and a C19 ubiquitin‐specific peptidase (C19 peptidase) domain. xref , xref To illustrate the molecular detail involved, co‐IP assays were performed in HEK‐293FT cells expressing Flag (vector), Flag‐USP22, Flag‐USP22 (1‒160 aa) or Flag‐USP22 (161‒525 aa) using anti‐Flag."
HPC affects USP22
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HPC increases the amount of USP22.
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"Hence, it is worth investigating whether HPC induces USP22 expression in CA1 to catalyze nuclear β-catenin deubiquitination, thereby promoting nuclear β-catenin stabilization and mediating neuroprotection against tGCI.Herein we aim to explore the mechanisms by which HPC regulates β-catenin ubiquitination to stabilize nuclear β-catenin in CA1 after tGCI."
HPC activates USP22.
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HPC inhibits USP22.
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sparser
"USP22 protein contains an N‐terminal zinc‐finger (ZnF) and a C19 ubiquitin‐specific peptidase (C19 peptidase) domain. xref , xref To illustrate the molecular detail involved, co‐IP assays were performed in HEK‐293FT cells expressing Flag (vector), Flag‐USP22, Flag‐USP22 (1‒160 aa) or Flag‐USP22 (161‒525 aa) using anti‐Flag."
reach
"Why USP22 has a preference for H2BK120ub as its substrate under Sorafenib treatment is worth further research.In summary, our study demonstrated that USP22 promotes the growth of hepatocellular carcinoma and resistance to Sorafenib‐induced ferroptosis by removing ubiquitin moieties from non‐histone protein CDK11B and histone H2B."
reach
"USP22 promotes the proliferation of hepatocellular carcinoma cells by stabilising CDK11B and enhances resistance to Sorafenib by inhibiting ferroptosis through the USP22/H2BK120ub/TFRC axis.So far, more than 40 USPs have been directly or indirectly associated with relevant cancer processes."
USP22 affects cell death
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USP22 activates cell death.
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USP22 inhibits cell death.
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USP22 inhibits cell death. 3 / 3
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"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 angiogenesis
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USP22 affects Wnt/β-catenin
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"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 affects NSCLC
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"Regardless, our data have identified and mapped interactions between PCAF and USP22, as well as further revealing the importance of the HAT and BRD domains of PCAF in mediating DNA damage signaling and repair of DSBs by HR.The observation of a H2BK120 ubiquitin to acetyl switch at DSBs (Clouaire et al. 2018) and the potential involvement of PCAF in mediating these events prompted us to test directly the involvement of PCAF in regulating H2BK120 acetylation."
USP22 affects AR-V7
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USP22 binds AR-V7.
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"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."
USP22 activates AR-V7.
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USP22 increases the amount of adenosine 5'-(pentahydrogen tetraphosphate).
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USP22 increases the amount of adenosine 5'-(pentahydrogen tetraphosphate). 6 / 6
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"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."
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"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."
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"Two weeks later, when the tumor size was approximately 100 mm , mice carrying USP22-overexpressing tumors were randomly divided into two groups (n = 4): siRNA of ZEB1 (7.5 μg) was injected into the tumor, and the other group was injected with the same amount of negative control every 72 h for another 2 weeks."
reach
"Regardless, our data have identified and mapped interactions between PCAF and USP22, as well as further revealing the importance of the HAT and BRD domains of PCAF in mediating DNA damage signaling and repair of DSBs by HR.The observation of a H2BK120 ubiquitin to acetyl switch at DSBs (Clouaire et al. 2018) and the potential involvement of PCAF in mediating these events prompted us to test directly the involvement of PCAF in regulating H2BK120 acetylation."
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 )."
USP22 affects pathway
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"SIRT1 has been reported to deacetylate PTEN and activate the PI3K/Akt/mTOR pathway. xref Deacetylated PTEN is well known to activate PI3K/AKT/mTOR pathway through promoting its phosphatase activity. xref , xref , xref To determine whether USP22 activates the PI3K/Akt/mTOR pathway via SIRT1‐mediated PTEN deacetylation, we used siRNA to silence the expression of SIRT1 in USP22‐overexpressing melanoma cells."
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"Therefore, high USP22 expression in tumor tissues could predict the benefit of sirolimus in patients with HCC after LT, which supports the significant role of USP22 in activating mTORC1 in HCC.In summary, in HCC, USP22 overexpression increased mTORC1 activity and sensitized HCC toward rapamycin."
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"Because USP22 was shown to activate mTORC1 activity, we hypothesized that USP22 interacts with certain proteins associated with mTORC1, including regulatory‐associated protein of mTOR (Raptor), mTOR‐associated protein, LST8 homolog (MLST8), mTOR, and FK506‐binding protein 12 (FKBP12)."
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"USP22 can reduce Ku70 acetylation by stabilizing SIRT1 expression, thereby inhibiting Bax-mediated apoptosis and promoting cisplatin resistance.ALDH1A3, a major ALDH isoenzyme, is important for the stem cell signature of lung cancer and is associated with enhanced cisplatin resistance in lung adenocarcinoma."
USP22 affects LINC01426
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USP22 affects ISG
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USP22 increases the amount of ISG.
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USP22 decreases the amount of ISG.
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"At present, the functional role of 3CLpro-mediated inactivation of RNF20 for H2Bub1 still remains to be addressed.Since loss of USP22 mostly affects type III IFN expression and secretion, USP22 likely mediates ISG expression both via epigenetic regulatory mechanisms as well as through long-term IFN-mediated priming effects in hIECs."
LINC01426 affects USP22
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"In addition, our immunofluorescence analysis showed that Importin-7 binds to AR or USP22 in both the nucleus and cytoplasm (Fig. 4C–E), suggesting that Importin-7 may regulate the nuclear translocation of AR and USP22.Next, we conducted a more in-depth study of the Importin-7–AR–USP22 complex by the treatment of AR inhibitor (enzalutamide) or AR ligands, including DHT and synthetic androgen R1881."
sparser
"EPI stimulation, which induced USP22 protein expression and promoted USP22-FOXO1 interaction, markedly inhibited FOXO1 polyubiquitination in USP22 WT cancer cells, and targeted USP22 deletion resulted in a significant increase in FOXO1 ubiquitination and reduced FOXO1 protein expression even with EPI stimulation ( xref )."
USP22 affects homologous recombination
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USP22 activates homologous recombination. 3 / 3
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USP22 activates homologous recombination. 3 / 3
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"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
"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 ] ."
reach
"Ultimately, we demonstrate that GSE1 is required for the recruitment of the deubiquitinase USP22 to the CoREST complex, potentially serving as a scaffold, and that loss of GSE1 inhibits deubiquitination of histone H2B at lysine 120, which was previously shown to facilitate γH2AX formation (11,35)."
sparser
"A previous MS study on HEK293T cells transfected with USP22 detected MYO1B as an interacting protein. [ xref ] MYO1B is a type of myosin and a motor protein involved in various biological processes, such as cell migration, cytoskeleton organization, and vesicle transport. [ xref ] Molecular docking simulations were performed to verify the interaction between USP22 and MYO1B (Figure xref )."
sparser
"About the possible relationship among BMI1 , EZH2 , and USP22 , it has been reported that USP22 increases BMI1 : in gastric cancer, USP22 inactivation decreases the neoplasm growth, while high levels of BMI1 accelerate the cell cycle via INK4a/ARF and AKT. xref Moreover, a reciprocal interaction between EZH2 and USP22 has been described in the sepsis‐induced myocardial dysfunction model: in this case, EZH2 represses USP22 through the H3K27me3 modification. xref In acute myeloid leukemia, the activation of BAX and the inhibition of BCL2 lead to a reduced expression of BMI1 and EZH2 . xref Finally, both BMI1 and EZH2 seem to be targets for the same miRNA, the miR200 that is a key regulator of the epithelial‐mesenchymal transition; indeed, a reduced expression of these genes reduces the migration capacity of colon cancer cells. xref "
USP22 affects Chromosomal Instability
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USP22 inhibits Chromosomal Instability. 6 / 6
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"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 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
"While the screen confirmed known substrates of USP22, including histones H2A and H2B, the sole component of the core cell cycle machinery identified as a USP22 substrate in this screen was the G1 phase cyclin CCND1.Further analysis of the USP22–CCND1 relationship revealed that USP22 directly reverses polyubiquitylation of CCND1 via a pathway distinct from protein-destabilizing GSK3β phosphorylation and ultimately protects CCND1 from proteasome-mediated degradation (16, 17)."
reach
"The elevated ubiquitylation and decreased steady-state levels of CCND1 seen after USP22 depletion suggest that deubiquitylation of CCND1 by USP22 may protect it from proteasomal degradation.Levels of both USP22 and CCND1 are elevated in human cancer, raising the possibility that elevated USP22 might protect CCND1 from degradation."
reach
"Collectively these findings support a model in which elevated expression of USP22 contributes to the aggressive growth of cancer cells in part via its ability to deubiquitylate and stabilize the rate-limiting cyclin CCND1, thereby promoting the G1–S transition.The identification of the USP22-CCND1 enzyme–substrate relationship may explain the previously reported phosphorylation-independent ubiquitylation and degradation of CCND1 (50)."
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
"Ultimately, we demonstrate that GSE1 is required for the recruitment of the deubiquitinase USP22 to the CoREST complex, potentially serving as a scaffold, and that loss of GSE1 inhibits deubiquitination of histone H2B at lysine 120, which was previously shown to facilitate γH2AX formation (11,35)."
sparser
"A previous MS study on HEK293T cells transfected with USP22 detected MYO1B as an interacting protein. [ xref ] MYO1B is a type of myosin and a motor protein involved in various biological processes, such as cell migration, cytoskeleton organization, and vesicle transport. [ xref ] Molecular docking simulations were performed to verify the interaction between USP22 and MYO1B (Figure xref )."
E3_Ub_ligase affects USP22
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Sphingosine-1-phosphocholine affects USP22
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Sphingosine-1-phosphocholine activates USP22.
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Sphingosine-1-phosphocholine activates USP22. 3 / 3
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"In light of these findings, it could be suggested that YAP1 silencing could reverse the protective effects of SPC on H/R-treated H9c2 cells.Altogether, our findings indicated that SPC up-regulated USP22, which stabilized KDM3A protein level via deubiquitination, and KDM3A inhibited H3K9me2 levels in the YAP1 promoter region to encourage YAP1 transcription, leading to reduction of MI/RI."
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."
Sphingosine-1-phosphocholine increases the amount of USP22.
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USP22 affects oxidative phosphorylation
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USP22 activates oxidative phosphorylation. 5 / 5
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"In terms of underlying mechanisms, RNA sequencing and gene ontology enrichment analysis demonstrated that USP22 knockout significantly suppressed angiogenesis, proliferation, EMT, RAS, c-Myc pathways, concurrently enhanced oxidative phosphorylation and tight junction pathways in A549 and H1299 NSCLC cells."
USP22 affects lipid catabolic process
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USP22 activates lipid catabolic process. 5 / 5
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"Future studies integrated with a psychologist team are needed to address this critical question.Our study revealed that USP22-mediated lipolysis circuit links the chronic stress–induced EPI production to breast cancer pathogenesis through the AKT-USP22-FOXO1-ATGL pathway across a wide range of human breast cancers, irrespective of their HER expression status."
USP22 affects gene expression
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USP22 activates gene expression. 5 / 5
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": not significant)and requests for resources and reagents should be directed to and 662 will be fulfilled by the corresponding author, Sjoerd J. L. van Wijk (vanWijk@med.uni-663 frankfurt.de; s.wijk@kinderkrebsstiftung-frankfurt.de)Profiling USP22-mediated gene expression in HT-29 hIECs."
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USP22 affects Sirt1/JAK/STAT3
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5
USP22 affects Parkinson Disease
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5
USP22 activates Parkinson Disease.
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3
USP22 deubiquitinates Parkinson Disease.
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2
USP22 affects PI3K/Akt/mTOR
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5
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"In addition, our immunofluorescence analysis showed that Importin-7 binds to AR or USP22 in both the nucleus and cytoplasm (Fig. 4C–E), suggesting that Importin-7 may regulate the nuclear translocation of AR and USP22.Next, we conducted a more in-depth study of the Importin-7–AR–USP22 complex by the treatment of AR inhibitor (enzalutamide) or AR ligands, including DHT and synthetic androgen R1881."
USP22 affects DNA repair
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USP22 affects Carcinoma, Non-Small-Cell Lung
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"19
However, there has been a lack of thorough investigation into the role of USP22 in hepatocellular carcinoma development and Sorafenib resistance.In this study, we demonstrate that USP22 promotes the proliferation of hepatocellular carcinoma cells by stabilising cyclin‐dependent kinase 11B (CDK11B)."
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
"It was recently shown that BLIMP1 enhances transcription of USP22 deubiquitinating enzyme leading to decreased degradation of SPI1 transcription factor and subsequent enhanced expression of programmed death ligand 1 (PD-L1), which leads to infiltrated CD8+ T cell exhaustion and memory responses [3]."
MiR-4490 affects USP22
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USP22 affects transcriptional regulator
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USP22 ubiquitinates transcriptional regulator.
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USP22 deubiquitinates transcriptional regulator.
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USP22 affects miR-34b
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USP22 affects miR-132-3p
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USP22 affects integrin b1
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"In addition, IHC staining of Ki‐67, H2BK120ub and TFRC in frozen sections from all four groups indicated that USP22 knockout promoted H2BK120ub and TFRC levels in transplanted tumours, and inhibited hepatocellular carcinoma malignancy as indicated by Ki‐67 staining, especially after Sorafenib treatment (Figure 8G‒J)."
USP22 affects Neoplastic Stem Cells
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4
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"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 MED1
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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."
USP22 affects Interferon
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4
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"More intriguingly, in A549 LUAD cells, immunoblot analysis with an antibody against ubiquitin (UB) after IP experiments using the anti‐COL17A1 antibody revealed that USP22 silencing resulted in a distinct increase in ubiquitinated COL17A1 protein level and COL17A1 degradation (Figure 5M), suggesting that USP22 induces the deubiquitination of the COL17A1 protein in LUAD cells."
USP22 affects AP4
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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."
MED1 affects USP22
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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."
Gal-SLPs affects USP22
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AR-V7 affects USP22
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"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."
AP4 affects USP22
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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."
MiR-144-3p affects USP22
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3
MiR-140 affects USP22
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Macrocycle affects USP22
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USP22 affects response to xenobiotic stimulus
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3
USP22 affects miR-144-3p
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3
USP22 affects lipid biosynthetic process
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USP22 affects fatty acid biosynthetic process
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USP22 affects extracellular matrix
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USP22 affects cellular survival
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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 ."
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 ) ."
USP22 affects cell stemness
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3
USP22 affects c-NHEJ
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3
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
"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]."
USP22 affects OS tumor growth
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USP22 affects LUAD
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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 USP22–KPNA2 axis in NF-κB activation after viral infection (data not shown)."
USP22 affects IFN-λ1
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3
USP22 affects Hypertrophy
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3
USP22 affects H2BK120ub
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USP22 affects DNA Damage
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USP22 affects CRPC
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sparser
"This Study demonstrated that targeting PCBP1-AS1 increases the sensitivity of prostate cancer cells to Enzalutamide by reducing the binding of USP22 to AR-V7 or AR and decreasing the stability of the complex, providing new ideas for the clinical treatment of drug-resistant patients with CRPC."
USP22 affects Aurora-B
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3
USP22 affects Adenocarcinoma of Lung
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3
USP22 affects AR-FL
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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 5-fluorouracil
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3
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
"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]."
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 USP22–KPNA2 axis in NF-κB activation after viral infection (data not shown)."
KLF3-AS1 affects USP22
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3
sparser
"This Study demonstrated that targeting PCBP1-AS1 increases the sensitivity of prostate cancer cells to Enzalutamide by reducing the binding of USP22 to AR-V7 or AR and decreasing the stability of the complex, providing new ideas for the clinical treatment of drug-resistant patients with CRPC."
AR-FL affects USP22
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3
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"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."
5-formyluracil affects USP22
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5-formyluracil activates USP22. 3 / 3
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"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
"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."
Chloroform affects USP22
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USP22 affects ubH2B
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USP22 affects tumor growth
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USP22 affects proteolysis
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USP22 affects evasion of host immune response
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USP22 affects conjugation
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USP22 affects cell quiescence
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USP22 affects cell cycle phase transition
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2
USP22 affects cell apoptosis
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1
USP22 affects SIRT1/AKT/MRP1
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2
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"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."
USP22 affects Proteasome
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USP22 activates Proteasome. 1 / 2
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USP22 affects NP
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USP22 affects NFATc1
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"These authors also reported down regulation of the Heat shock protein family A (Hsp70) member 5 (HSPA5), an HSP70 family member involved in the unfolded protein response, in tumors from Usp22 null mice, consistent with reports that USP22 mediates deubiquitination of HSPA5 in human prostate cancer cells [15]."
USP22 affects H2Aub1
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2
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"We found that USP22 knockdown could inhibit the glycolytic pathway in osteosarcoma cells, suppress cell proliferation, migration and invasion, and promote cancer cell apoptosis.Glycolysis is one of the major pathways for cells to generate energy by converting glucose into lactate and producing ATP (Lunt & Vander Heiden, 2011)."
USP22 affects AR-V7 protein
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USP22 affects ADR
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USP22 affects 5-formyluracil
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USP22 inhibits 5-formyluracil. 2 / 2
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SNHG16 affects USP22
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Reactive Oxygen Species affects USP22
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NP affects USP22
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NFATc1 affects USP22
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"We observed over branching of the mammary glands in USP22 overexpressing mice, along with aberrant up regulation of many of the same signaling pathways that were down regulated in Usp22 null embryos, including estrogen receptor, extracellular signal-regulated kinase /Mitogen-activated protein kinase (ERK/MAPK), and TGFβ signaling [16, 17]."
Lentivirus Infections affects USP22
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FO affects USP22
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2
Atx7 affects USP22
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2
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2