IndraLab

Statements



reach
"For example, USP39 promotes cell cycle, and proliferation, resulting in the development of leukemia [6] ."

reach
"USP39 silencing via lentivirus mediated short hairpin RNA (shRNA) significantly suppressed melanoma cell proliferation, induced G0/G1 cell cycle phase arrest, and increased apoptosis in vitro."

reach
"Knockdown of USP39 expression in HCC can significantly inhibit cell proliferation, resulting in cell cycle arrest at the G2/M phase [62]."

reach
"The de-acetylation of USP39 by SIRT7 can promote its stability and thereby accelerate HCC cell proliferation and tumorigenesis."

reach
"In human liver cancer cells, USP39 promoted tumor proliferation in a spliceosome-dependent manner."

reach
"In summary, USP39 significantly promotes the proliferation of HCC cells and enhances their capacity for invasion and metastasis through mechanisms that include the regulation of the Wnt/β-catenin signaling pathway, metabolic reprogramming, and EMT."

reach
"Unlike wild-type USP39, which rescued the inhibitory effect of USP39 deficiency on cell proliferation and cell cycle progression, the C139A mutant could not reverse the suppressive effects (Figs."

reach
"Zhao et al. further indicated that USP39 promoted the proliferation of ESCC cells by enhancing the splicing and maturation of Rictor mRNA, a component of the mTOR complex, and regulating the mTORC2 signaling pathway [50]."

reach
"miR-133a, directly targeted USP39, suppresses cell proliferation and predicts prognosis of gastric cancer."

reach
"The depletion of USP39 could inhibit the proliferation and metastasis of HCC cells [11]."

reach
"USP39 downregulation could inhibit RCC cell proliferation and progression, suggesting that USP39 may prove to be a potential target for inhibiting RCC."

reach
"Knockdown of USP39 significantly inhibited proliferation of TT cells in vitro."

reach
"Knockdown of USP39 suppressed the proliferation and cell cycle progression, and induced apoptosis, accompanied by the reduction of EGFR in both mRNA and protein levels in PC-3 and DU145 cells."

reach
"Downregulation of ubiquitin-specific peptidase 39 suppresses the proliferation and induces the apoptosis of human colorectal cancer cells."

reach
"Down-regulation of USP39 suppresses the proliferation and induces the apoptosis of human colorectal cancer cells [XREF_BIBR]."

sparser
"Furthermore, knockdown of USP39 inhibited VSMC cell proliferation and the expression of cyclin D1 and cyclin-dependent kinase 4, as analyzed via cell counting, MTT assay and western blotting."

reach
"Downregulation of USP39 significantly reduces the proliferation and colony-forming ability of triple-negative breast cancer cells [65, 67]."

reach
"Subsequent studies will be required to verify whether the inhibition of STAT1 is responsible for the inhibition of gastric cancer cell proliferation by USP39 siRNA.The article also has some limitations, as the role of USP39 has not been validated in animal models."

reach
"Functionally, si‐USP39 suppressed the proliferation (Figure 4B,C), triggered the apoptosis (Figure 4D,E), and impaired the invasion (Figure 4F,G) in H1299 and A549 cells."

reach
"USP37 promotes S phase entry by activating CDK2 and regulates cell proliferation by stabilizing p27 ( Huang et al., 2011 ; Das et al., 2013 ), and USP39 inhibits malignant proliferation of several tum[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 63
| 47

reach
"The inhibition of USP39 can induce G2/M phase arrest and promote apoptosis (Huang et al., 2016)."

reach
"Mechanism study showed that USP39 knockdown induced the arrest of cell cycle and apoptosis of leukemia cells."

reach
"USP39 silencing via lentivirus mediated short hairpin RNA (shRNA) significantly suppressed melanoma cell proliferation, induced G0/G1 cell cycle phase arrest, and increased apoptosis in vitro."

reach
"Conversely, overexpression of USP39 attenuates apoptosis in RKO cells."

reach
"FCM assay showed that USP39 knockdown led to G2/M arrest and induced apoptosis in the HepG2 cells."

reach
"Furthermore, we demonstrate that USP39 depletion promotes apoptosis induced by cisplatin, which is related with the induction of oxidative stress and DNA damage response."

reach
"Knockdown of USP39 inhibited the growth of osteosarcoma cells and induced apoptosis in vitro [XREF_BIBR]."

reach
"Indeed, knockdown of USP39 induces cell cycle arrest and apoptosis in melanoma [XREF_BIBR]."

reach
"Furthermore, USP39 silencing induced apoptosis of CAL27 cells via activations of Caspase 3 and PARP."

reach
"Silencing of USP39 induced cell apoptosis and cell cycle arrest at G2/M phase."
| 16

reach
"Previous studies have reported that USP39 silencing inhibits colon cancer cell growth and metastasis, and induces apoptosis by regulating the Wnt/β-catenin signaling pathway [31]."

reach
"Second, we found that knocking down USP39 induces apoptosis of A549 and HCC827 cells, upregulates cleaved cas3, cleaved cas9 and DNA damage makers (53BP1 and gammaH2AX) [XREF_BIBR]."

reach
"Knockdown of USP39 suppressed the proliferation and cell cycle progression, and induced apoptosis, accompanied by the reduction of EGFR in both mRNA and protein levels in PC-3 and DU145 cells."

reach
"However, co-expressing Cyclin B1 failed to rescue the accelerated apoptosis of glioma cells induced by the downregulation of USP39 in glioma cells, suggesting the Cyclin B1 only affect the cell proliferation by regulating the cell cycle (data not shown)."

reach
"Moreover, we transfected Flag‐MRPL35 and si‐NC or si‐USP39 into 293 T cells and found that USP39 silencing enhanced MRPL35 ubiquitination (Figure 3H).3.4 USP39 Knockdown Suppresses NSCLC Cell Proliferation, Invasion, and Glutamine Metabolism and Induces Cell Apoptosis by MRPL35."

reach
"Depletion of USP39 promotes apoptosis of U2OS cells."

reach
"Downregulation of ubiquitin-specific peptidase 39 suppresses the proliferation and induces the apoptosis of human colorectal cancer cells."

reach
"Furthermore, previous studies have shown that USP39 as an important regulator of the susceptibility to drug-induced apoptosis."

reach
"Down-regulation of USP39 induced SMMC-7721 cells apoptosis."

reach
"The group of silencing USP39 increased the apoptotic cells (early apoptosis and late apoptosis) by 13-fold, as compared to the group of shCon (Additional file 1 : Figure S1A and B)."
USP39 affects cell cycle
| 33
USP39 activates cell cycle.
| 17
| 17

reach
"First, we observed that depletion of USP39 contributes to abnormal cell cycle distribution by inducing cell cycle arrest at G2/M."

reach
"Taken together, these results suggest that knockdown of USP39 could inhibit TT cell proliferation by inducing G2/M phase cell cycle arrest."

reach
"In addition, it has been reported that overexpression of MGC-803 cells and knockdown of USP39 may inhibit MGC-803 cell proliferation and induce cell cycle arrest."

reach
"Taken together, our findings implicate that USP39 promotes the development of human leukemia by regulating cell cycle, survival, and proliferation of the cells."

reach
"Furthermore, suppression of USP39 arrested cell cycle progression at G 2 / M phase in SMMC-7721cells."

reach
"Knockdown of endogenous USP39 expression could suppress the oncogenic properties of osteosarcoma cells and induce cell cycle arrest at G2/M phase, promote apoptosis through PARP cleavage."

reach
"This observation indicated that the cell cycle was blocked at the G2/M phase by USP39 knockdown in HL-60 cells (XREF_FIG A, B)."

reach
"USP39 knockdown inhibits cell cycle progression."

reach
"Knockdown of USP39 significantly decreased cell proliferation and caused cell cycle arrest at G2/M phase."

reach
"Knockdown of USP39 induced cell cycle arrest and its effect on cell cycle-regulatory molecules."
USP39 inhibits cell cycle.
| 16
| 16

reach
"Silencing of USP39 induced cell apoptosis and cell cycle arrest at G2/M phase."

reach
"Mechanism study showed that USP39 knockdown induced the arrest of cell cycle and apoptosis of leukemia cells."

reach
"This indicates that USP39 shRNA could strongly block (p < 0.01) the cell cycle progression of TT cells."

reach
"Knockdown of USP39 suppressed the proliferation and cell cycle progression, and induced apoptosis, accompanied by the reduction of EGFR in both mRNA and protein levels in PC-3 and DU145 cells."

reach
"To evaluate the role of cell cycle-regulatory molecules in knockdown of USP39 induced G2/M cell cycle arrest, we examined the effect of USP39 knockdown on cell cycle-regulatory molecules, including p21, CDK1 and cyclin A2."

reach
"USP39 silencing via lentivirus mediated short hairpin RNA (shRNA) significantly suppressed melanoma cell proliferation, induced G0/G1 cell cycle phase arrest, and increased apoptosis in vitro."

reach
"Similarly, we observed that USP39 knockdown induced cell cycle arrest at G2/M phase in Jurkat cells (XREF_FIG C, D)."

reach
"Flow cytometric analysis showed that USP39 knockdown induced cell cycle arrest at G2/M phase and enhanced cell apoptosis in 95D cells."

reach
"Our loss-of-function experiments demonstrated that knockdown of the expression of USP39 repressed the proliferation of leukemia cells, induced cell cycle arrest, and cell apoptosis."

reach
"However, treated with PFT-alpha reduced the up-regulation of p21 and BAX induced by USP39 knockdown, but had no effect on the down-regulation of cell cycle related proteins (CDK1 and CyclinB1 and CDK2 and CyclinA2) induced by USP39 knockdown."
USP39 affects HYCC1
| 31
USP39 activates HYCC1. 10 / 31
| 31

reach
"USP39 promotes HCC cell proliferation and migration by deubiquitinating β-catenin, activating WNT/β-catenin signaling pathway [12]."

reach
"USP39 stabilizes beta-catenin by deubiquitination and suppressing E3 ligase TRIM26 pre-mRNA maturation to promote HCC progression."

reach
"USP39 promotes the malignant progression of HCC [60, 61] (Fig. 2)."

reach
"However, the molecular mechanism by which USP39 promotes HCC progression has not been well defined, especially regarding its putative ubiquitination function."

reach
"In HCC, SIRT7-mediated deacetylation impedes MYST1-facilitated acetylation of USP39, which is a prerequisite for its E3 ligase-induced degradation [55] and accelerates the tumorigenesis of HCC."

reach
"The de-acetylation of USP39 by SIRT7 can promote its stability and thereby accelerate HCC cell proliferation and tumorigenesis."

reach
"In summary, USP39 significantly promotes the proliferation of HCC cells and enhances their capacity for invasion and metastasis through mechanisms that include the regulation of the Wnt/β-catenin signaling pathway, metabolic reprogramming, and EMT."

reach
"Moreover, USP39 depletion inhibits HCC cell proliferation and metastasis by promoting ZEB1 degradation."

reach
"Here, we prove that USP39 promotes HCC cell proliferation and migration by directly deubiquitin beta-catenin, a key molecular of Wnt/beta-catenin signaling pathway whose abnormal expression or activation results in several tumors, following its co-localization with USP39."

reach
"The mRNA level of USP39 was significantly elevated in HCC."
USP39 affects CCNB1
5 | 13 12
USP39 binds CCNB1.
5 | 3 11
5 | 3 11

sparser
"Our findings suggest that USP39-Cyclin B1 axis may function as the potential therapeutic target for the treatment of human glioma."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"Co-immunoprecipitation and other assays were performed to detect the interacting of Cyclin B1 and USP39."

reach
"Next, we sought to detect an interaction of Cyclin B1 and USP39."

reach
"Additionally, the interaction between endogenous USP39 and Cyclin B1 in U87 cells was demonstrated by anti-Cyclin B1 immunoprecipitation (Fig. 2e)."

sparser
"USP39 interacts with Cyclin B1 and stabilizes its expression by deubiquitinating Cyclin B1."
USP39 activates CCNB1.
| 4
USP39 activates CCNB1. 4 / 4
| 4

reach
"USP39 mediates p21 dependent proliferation and neoplasia of colon cancer cells by regulating the p53/p21/CDC2/cyclin B1 axis."

reach
"Taken together, these results suggest that USP39 knockdown promotes Cyclin B1 protein degradation in a proteasome-dependent manner."

reach
"We found that USP39 could upregulate Cyclin B1 protein stability to promote G2/M cell cycle transition and glioma cell proliferation, as well as tumor growth in vivo."

reach
"A cycloheximide (CHX) chase assay in U251 and U87 cells showed that knockdown of USP39 decreased the half-life of Cyclin B1 (Fig. 1j), and upregulation of USP39 increased the half-life of Cyclin B1 (Fig. 1k)."
USP39 increases the amount of CCNB1.
| 3
USP39 increases the amount of CCNB1. 3 / 3
| 3

reach
"Moreover, in other human tumor cell lines, such as A549, MDA-MB-231 and SW480, knockdown of USP39 could also downregulate Cyclin B1 expression (Fig. S2)."

reach
"In HEK293T and U87 cells, overexpression of USP39 could increase Cyclin B1 protein level (Fig. 1e and f)."

reach
"In addition, USP39-overexpressed U87 cells exhibited increased Cyclin B1 protein levels and the number of Ki67 positive tumor cells by IHC analyses (Fig. 5j)."
USP39 phosphorylates CCNB1.
| 1 1
USP39 leads to the phosphorylation of CCNB1. 2 / 2
| 1 1

sparser
"Mechanistic analyses indicate that USP39 promotes the phosphorylation of AKT, EGFR, and cyclin B1, while it deters the activation of PARP and Caspase-3, thereby enhancing cell proliferation, migration, and invasion, and curbing apoptosis [ xref ]."

reach
"Mechanistic analyses indicate that USP39 promotes the phosphorylation of AKT, EGFR, and cyclin B1, while it deters the activation of PARP and Caspase-3, thereby enhancing cell proliferation, migration, and invasion, and curbing apoptosis [78]."
USP39 decreases the amount of CCNB1.
| 1
USP39 decreases the amount of CCNB1. 1 / 2
| 1

reach
"Conversely, knockdown of USP39 in U87 cells increased the endogenous ubiquitination levels of Cyclin B1 (Fig. 3b)."
USP39 deubiquitinates CCNB1.
| 1
USP39 deubiquitinates CCNB1. 1 / 1
| 1

reach
"To understand the functional significance of the interaction between USP39 and Cyclin B1, we assessed whether USP39 deubiquitinated Cyclin B1 in cells."
USP39 affects Neoplasms
| 4 26
USP39 activates Neoplasms.
| 4 19
| 4 19

reach
"Specifically, USP39 promotes breast cancer cell proliferation and tumor growth by deubiquitinating and stabilizing the transcription factor FOXM1 [31]."

reach
"Here, we prove that USP39 promotes HCC cell proliferation and migration by directly deubiquitin beta-catenin, a key molecular of Wnt/beta-catenin signaling pathway whose abnormal expression or activation results in several tumors, following its co-localization with USP39."

reach
"Mainly, in the first group, we have genes with a suggested novel anti-cancer role in the testis (Fetub, Hoxd10, Slc45a3, Ube2l6), with increased expression levels inhibiting cancer cell development, supported by the protective role of Mt3; while the Usp39 gene, with elevated expression levels (the most of all the observed changes), should lead to some tumor-like changes within the testis tissue."

reach
"In human liver cancer cells, USP39 promoted tumor proliferation in a spliceosome-dependent manner."

reach
"Mechanically, histone lactylation stimulated USP39 expression to promote tumor progression."

reach
"To delve into the contribution of GLI1 in the tumor-promoting effects of USP39, we generated A549 and H1299 cell lines with stable GLI1 knockdown in conjunction with USP39 overexpression (Fig. 6C), and then performed MTT, colony formation, and transwell assays to examine the influence on cell growth and migration."

reach
"Consistently, tumor weights from USP39 downregulation group were drastically decreased, while USP39 complementation led to increased tumor mass significantly (Fig. 7B, C)."

reach
"In addition, overexpression of USP39 accelerated the tumor growth and reversed the 2-DG-caused tumor inhibition (Fig. 6A–C)."

reach
"Importantly, silencing of USP39 significantly suppressed tumor growth in vitro and in vivo study [9,10] ."

reach
"Therefore, our study reveals the LLPS characteristics of USP39 and its nucleolar association, thus providing a novel perspective to investigate the tumor-promoting functions of USP39."
USP39 inhibits Neoplasms.
| 7
| 7

reach
"The downregulation of USP39 expression in HCC cells significantly inhibited tumor growth, by reducing the volume and weight of tumors (Fig. 8A–C)."

reach
"Gan et al. demonstrated that USP39 expression was overexpressed in osteosarcoma and that USP39 knockdown arrested osteosarcoma cells in G2/M phase, thereby inhibiting tumor growth and metastasis (104)."

reach
"We then examined whether the EC tumor suppression effect of the treatment with the histone lactylation inhibitor 2-DG could be reversed by increased USP39 levels."

reach
"USP37 promotes S phase entry by activating CDK2 and regulates cell proliferation by stabilizing p27 ( Huang et al., 2011 ; Das et al., 2013 ), and USP39 inhibits malignant proliferation of several tum[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Histone lactylation and USP39 promote EC development, and USP39 overexpression reverses the suppression of tumor growth by 2-DG in vivo."

reach
"These in vivo results are in accordance with our in vitro data, suggesting that USP39 functions as a tumor-promoting DUB and USP39 knockdown elicits suppressive effects on lung cancer growth by downregulating GLI1."

reach
"Knockdown of USP39 could inhibit the proliferation and induce apoptosis of SMMC-7721 cells, as well as the growth of xenograft tumors in nude mice."
USP39 affects ETS2
| 19 9
USP39 binds ETS2.
| 6 9
| 6 9

sparser
"Strategies that promote the interaction between USP39 and ETS2 may offer new avenues for precise therapeutic interventions."

sparser
"Additionally, USP39 can interact with ETS2 via its N-terminal region, thereby regulating the transcriptional activity of ETS2 ( xref )."

sparser
"USP39 interacts with ETS2 through their respective amino-terminal regions, and the zinc finger and PNT domains are not required for this binding."

sparser
"ETS2 Interacts with USP39 through the Respective Amino-Terminal Regions."

sparser
"To identify the domains responsible for the interaction between ETS2 and USP39, we created several deletion mutants of ETS2:ΔETS (ETS domain-deleted, aa 1–362), PNT-only (Pointed domain-containing, aa 1–170), ΔPNT (Pointed domain-deleted, aa 1–84 & 171–469) and 171–362 (containing aa 171–362) ( xref A)."

reach
"Based on the mutual binding affinity between USP39 and the substrate protein ETS2, as well as its influence on the transcriptional activity of ETS2, we selected USP39 as the candidate DUB for ETS2 and proceeded with further characterization."

sparser
"The results demonstrated that USP39 could bind to ETS2 and all its mutants except 171–362."

sparser
"These findings confirm that USP39 binds to the unspecified amino-terminal region of ETS2, and they indicate that the PNT domain is not required for their interaction."

reach
"To identify the domains responsible for the interaction between ETS2 and USP39, we created several deletion mutants of ETS2:ΔETS (ETS domain-deleted, aa 1–362), PNT-only (Pointed domain-containing, aa 1–170), ΔPNT (Pointed domain-deleted, aa 1–84 & 171–469) and 171–362 (containing aa 171–362) (Figure 3A)."

sparser
"We then examined the interaction between ETS2 and USP39 and USP39 mutants."
USP39 inhibits ETS2.
| 6
USP39 inhibits ETS2. 6 / 6
| 6

reach
"USP39 Represses the Transcriptional Activity of ETS2 Partly by Suppressing Its Nuclear Localization."

reach
"This indicates that USP39 strongly suppresses the nuclear localization of ETS2."

reach
"This result clearly suggests that USP39 antagonizes the transcriptional activity of ETS2, which may be partly due to the reduced nuclear localization caused by the deubiquitination of ETS2."

reach
"Interestingly, however, USP39 significantly suppresses the transcriptional activity of ETS2."

reach
"USP39 Interacts with and Suppresses Transcriptional Activity of ETS2."

reach
"USP39 suppressed the transcription activity of ETS2 by approximately 72.8%, while OTUD7A and OTUD7B increased the transcription activity of ETS2 by approximately 55.2% and 68.5%, respectively."
USP39 deubiquitinates ETS2.
| 6
USP39 deubiquitinates ETS2. 6 / 6
| 6

reach
"USP39 deubiquitinates ETS2 without affecting its protein stability."

reach
"USP39 Deubiquitinates ETS2 but Does Not Affect Its Protein Stability."

reach
"Since ETS2 is targeted for proteasomal degradation through ubiquitination via the E3 ubiquitin ligase COP1 [8,14,15], we investigated whether USP39 deubiquitinates ETS2 and regulates its protein stability."

reach
"As depicted in Figure 4A, USP39 noticeably deubiquitinates the polyubiquitin chains of ETS2."

reach
"USP39 deubiquitinated both the mono- and polyubiquitination of endogenously ubiquitinated ETS2.Although ETS2 was deubiquitinated by USP39, the protein stability of ETS2 did not show substantial changes over the 30 h period in this study (Figure 4C,D)."

reach
"Subsequently, we found that USP39 deubiquitinates ETS2 and suppresses its transcriptional activity."
USP39 decreases the amount of ETS2.
| 1
USP39 decreases the amount of ETS2. 1 / 1
| 1

reach
"Surprisingly, the increased USP39 dramatically and statistically significantly reduced ETS2 protein levels in the nucleus (from 1.00 in GFP control to approximately 0.04 in USP39), while causing only marginal changes in the cytoplasmic fraction (from 1.00 in GFP control to approximately 0.99 in USP39) (Figure 5A,B)."
SIRT7 affects USP39
6 | 15 6
SIRT7 binds USP39.
6 | 2 6
6 | 2 6

sparser
"Moreover, Dong et al.’s study revealed that USP39 interacts with SIRT7, which deacetylates USP39 to enhance its stability, thereby further promoting HCC development ( xref )."

No evidence text available

No evidence text available

No evidence text available

sparser
"The results of Co-IP revealed that Flag-USP39 was significantly enriched in the precipitates of Myc-SIRT7 and vice versa, which indicated that USP39 interacted with SIRT7 in CaSki and SiHa cells (Fig.  xref B)."

No evidence text available

No evidence text available

reach
"The binding between USP39 and SIRT7 was evaluated by western blot using anti-Flag tag (ab205606, 1/3000, abcam) or anti-Myc (ab32, 1/3000, abcam) antibodies."

sparser
"In addition, we also evaluated the interaction between SIRT7 and USP39 in human CSCC tissues."

sparser
"Co-immunoprecipitation indicated that SIRT7 interacted with USP39 (Additional file xref : Fig S2A)."
SIRT7 deacetylates USP39.
| 6
SIRT7 deacetylates USP39. 6 / 6
| 6

reach
"SIRT7 interacts with and mediates USP39 deacetylation."

reach
"In addition, SIRT7 deacetylates USP39 to promote its protein stability and enhance autophagy, while inhibiting ROS production in CSCC cells [33]."

reach
"A previous study suggested that SIRT7 promoted the deacetylation of USP39 in hepatocellular carcinoma cells [24]."

reach
"USP39 was deacetylated by SIRT7 and promoted SIRT7 expression by facilitating FOXM1-mediated SIRT7 transcription."

reach
"The de-acetylation of USP39 by SIRT7 can promote its stability and thereby accelerate HCC cell proliferation and tumorigenesis."

reach
"The deacetylation of USP39 by SIRT7 promotes the stability and thereby accelerates cell proliferation and tumorigenesis of HCC [10] ."
SIRT7 activates USP39.
| 6
SIRT7 activates USP39. 6 / 6
| 6

reach
"Besides, SIRT7 promotes autophagy and inhibits oxidative stress in cervical squamous cell carcinoma cells by regulating the USP39/FOXM1 axis [23]."

reach
"SIRT7 promotes USP39 protein stability via deacetylation at the site K428, and USP39 facilitates the splicing efficacy of FOXM1 to elevate FOXM1 expression."

reach
"Moreover, SIRT7 has been demonstrated to deacetylate USP39, increasing the stability, and promoting the oncogenic activity of USP39 in hepatocellular carcinoma development [24]."

reach
"These results indicate that SIRT7 promotes the stability of USP39 via deacetylation."

reach
"In the above experiment, we have shown that SIRT7 interacts with USP39 and enhance protein stability of USP39 via deacetylation and that USP39 regulates SIRT7 expression."

reach
"Furthermore, SIRT7 increases the stability of USP39 by means of direct deacetylation."
SIRT7 inhibits USP39.
| 1
SIRT7 inhibits USP39. 1 / 1
| 1

reach
"Rescue assays also indicated that SIRT7 promoted autophagy and inhibited ROS production in CSCC cells by regulating USP39/FOXM1."
| 4 22
| 4 20

reach
"Studies have shown that USP39 knockout inhibits the migration and invasion of colon cancer cells."

reach
"We reported similar results in our previous study, in which knockdown of USP39 suppressed the glioma cell migration and invasion in vitro and inhibited glioma growth and invasion in vivo [12]."

reach
"USP39 level was higher in hypoxia-induced hRMECs, functionally, USP39 silencing reversed hypoxia-induced migration, invasion and angiogenesis in hRMECs."

reach
"Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism."

reach
"In summary, USP39 significantly promotes the proliferation of HCC cells and enhances their capacity for invasion and metastasis through mechanisms that include the regulation of the Wnt/β-catenin signaling pathway, metabolic reprogramming, and EMT."

reach
"USP39 promotes proliferation and invasion in vitro and tumor growth in vivo."

reach
"USP39 increases proliferation and invasion of ovarian cancer cells and promotes growth of xenograft tumors in mice."

reach
"Moreover, we transfected Flag‐MRPL35 and si‐NC or si‐USP39 into 293 T cells and found that USP39 silencing enhanced MRPL35 ubiquitination (Figure 3H).3.4 USP39 Knockdown Suppresses NSCLC Cell Proliferation, Invasion, and Glutamine Metabolism and Induces Cell Apoptosis by MRPL35."

reach
"In addition, a transwell invasion assay revealed that forced expression of USP39 significantly enhanced the invasion capacity whereas knockdown of USP39 decreased the invasion potential of ovarian cancer cells."

reach
"In glioma, USP39 acts as a splicing factor by altering the 3ʹ splice site to increase the expression of high mobility group protein A2 (HMGA2) and promotes the maturation of migratory invasion-associated proteins and TAZ mRNA, a key protein in the ADAM9 and Hippo signaling pathways."

reach
"We reported similar results in our previous study, in which knockdown of USP39 suppressed the glioma cell migration and invasion in vitro and inhibited glioma growth and invasion in vivo [12]."

reach
"Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro."
USP39 is modified
14 | 1 10
USP39 is phosphorylated.
13 |
USP39 is phosphorylated on S82. 8 / 8
8 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP39 is phosphorylated on S46. 3 / 3
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 is phosphorylated on S97. 1 / 1
1 |

No evidence text available
USP39 is phosphorylated on T357. 1 / 1
1 |

No evidence text available
USP39 is acetylated.
1 | 8
USP39 is acetylated. 8 / 8
| 8

sparser
"After treatment with histone deacetylase (HDAC) inhibitor TSA or SIRT inhibitor NAM, USP39 acetylation level exhibited a significant elevation."

sparser
"Then acetylation level of USP39 was also examined under the transfection of sh-SIRT7 in CaSki cells, and the results demonstrated that USP39 acetylation levels were significantly elevated by sh-SIRT7 (Fig.  xref D)."

sparser
"Further analysis revealed that USP39 acetylation was inhibited by wild type SIRT7, and the mutant SIRT7 without USP39 acetylation activity (SIRT7 H187Y) was demonstrated to suppress USP39 deacetylation (Fig.  xref E)."

sparser
"Conversely, the lysine deacetylase sirtuin 7 (SIRT7) removes the acetylation of USP39, promoting its stability and consequently accelerating the proliferation and tumorigenesis of HCC cells both in vitro and in vivo xref ."

sparser
"Acetylated USP39 can be degraded by E3 ubiquitin ligase (VHL)-mediated proteasome ( xref )."

sparser
"Previously, it was reported that USP39 could be acetylated by histone acetyltransferase MYST1, and the acetylated USP39 was subsequently degraded by E3 ubiquitin ligase VHL-mediated proteasomal degradation."

sparser
"In HCC, SIRT7-mediated deacetylation impedes MYST1-facilitated acetylation of USP39, which is a prerequisite for its E3 ligase-induced degradation [ xref ] and accelerates the tumorigenesis of HCC."

sparser
"Therefore, we assessed if USP39 acetylation was affected by SIRT7 in cervical cancer cells."
USP39 is acetylated on K428. 1 / 1
1 |

No evidence text available
USP39 is sumoylated.
| 2
USP39 is sumoylated. 2 / 2
| 2

sparser
"Inhibition of SUMOylation of USP39 enhanced the proliferation of cancer cells as it affected the recruitment of tri-snRNP, suggesting that SUMOylation of USP39 plays an essential role in cancer therapy ( xref ; xref )."

sparser
"Furthermore, inhibition of the SUMOylation of USP39 can enhance the proliferation of cancer cells including breast and hepatocellular cancer via affecting the recruitment of tri-snRNP, suggesting that SUMOylation of USP39 has an essential role in cancer therapy ( xref ; xref ; xref ) ( xref )."
USP39 is deacetylated.
| 1
USP39 is deacetylated. 1 / 1
| 1

reach
"Further analysis revealed that USP39 acetylation was inhibited by wild type SIRT7, and the mutant SIRT7 without USP39 acetylation activity (SIRT7 H187Y) was demonstrated to suppress USP39 deacetylation (Fig. 3E)."
USP39 affects ZEB1
1 | 20 3
USP39 increases the amount of ZEB1.
| 6
USP39 increases the amount of ZEB1. 6 / 6
| 6

reach
"It is interesting to speculate that whether E3 ligase TRIM26 with ubiquitin function has a common foothold with USP39, that is, TRIM26 affects the stability of ZEB1 through ubiquitination, while USP39 promotes the abnormality of ZEB1 level through deubiquitination, which orchestrates the occurrence of EMT and determines the progression of HCC.This study uncovers the elaborate ubiquitination and deubiquitination modifications of ZEB1 in HCC."

reach
"Accordingly, the protein level of ZEB1 could be increased by USP39 overexpression in SK-hep-1 cell (Fig. 3B)."

reach
"In our study, similarly, USP39 can modulate the level of ZEB1 protein via deubiquitination."

reach
"Our results revealed that the silencing of USP39 expression significantly suppressed ZEB1 protein expression in SK-hep-1 and HepG2 cells (Fig. 3A)."

reach
"Collectively, these results revealed a functional significance of USP39 on the ZEB1 induced EMT progression in HCC at protein levels.Interestingly, the ZEB1 mRNA level showed no significant difference in HepG2 cells transduced with shUSP39 (Fig. S2), which indicated that USP39 may mediate ZEB1 expression via posttranslational regulation (i.e., protein deubiquitination)."

reach
"Since ubiquitination and stability play important roles in ZEB1 regulation, hypothetically, USP39 with the function of deubiquitination could promote HCC progression through regulating the level of ZEB1 ubiquitination.The tripartite motif (TRIM) family proteins possess one or two B-boxes along with its domain structure, and a more diverse domain at the C terminus [20, 21], which are considered key regulators of protein degradation through ubiquitylation."
USP39 deubiquitinates ZEB1.
1 | 5
USP39 deubiquitinates ZEB1. 6 / 6
1 | 5

reach
"In consideration of ZEB1 deubiquitination by USP39, we wondered if there were other protein participates in HCC development, which could be simultaneously regulated by USP39 and TRIM26."

reach
"Collectively, our findings suggest that the balanced deubiquitination and ubiquitination of ZEB1 by USP39 and TRIM26 represent a novel mechanism for the progression of HCC, and this discovery provides a promising strategy for targeting USP39 or TRIM26 in the treatment of HCC cases with aberrant ZEB1 expression levels."

reach
"USP39 promotes EMT and inhibits ZEB1 ubiquitination in HCC."

reach
"Mechanistically, TRIM26 ubiquitinates and targets ZEB1 for degradation, while USP39 deubiquitinates and stabilizes ZEB1 to promote hepatocellular carcinoma (HCC) [86]."

reach
"Other studies have shown that Ubiquitin-specific peptidase 39 (USP39) deubiquitinates and suppresses ZEB1 degradation, thus promoting the development of EMT and the onset of hepatocellular carcinoma."

"Deubiquitinase <span class="match term0">USP39</span> and E3 ligase TRIM26 balance the level of <span class="match term1">ZEB1</span> ubiquitination and thereby determine the progression of hepatocellular carcinoma"
USP39 decreases the amount of ZEB1.
| 3
USP39 decreases the amount of ZEB1. 3 / 3
| 3

reach
"Conversely, USP39 knockdown significantly reversed the ZEB1 protein level in SK-hep-1 after transfection with shTRIM26 (Fig. 7H)."

reach
"This hypothesis was further corroborated by the fact that USP39 could reverse the effect of TRIM26 on ZEB1 expression and the progression of HCC."

reach
"In addition, USP39 downregulation dramatically suppressed the level of ZEB1 as well as EMT progression."
USP39 binds ZEB1.
| 3
| 3

sparser
"Co-immunoprecipitation assays demonstrated the formation of a complex between endogenous USP39 and ZEB1 proteins in OPM2 cells (Fig.  xref F)."

sparser
"It was previously reported that USP5 promotes HCC progression by stabilizing SLUG xref , while USP39 interacts with ZEB1 and regulates HCC proliferation xref ."

sparser
"To elucidate whether USP39 modulates the ubiquitination status of ZEB1, we initially examined the interaction between the USP39 enzyme and its substrate ZEB1."
USP39 ubiquitinates ZEB1.
| 2
USP39 leads to the ubiquitination of ZEB1. 2 / 2
| 2

reach
"Since ubiquitination and stability play important roles in ZEB1 regulation, hypothetically, USP39 with the function of deubiquitination could promote HCC progression through regulating the level of ZEB1 ubiquitination.The tripartite motif (TRIM) family proteins possess one or two B-boxes along with its domain structure, and a more diverse domain at the C terminus [20, 21], which are considered key regulators of protein degradation through ubiquitylation."

reach
"Clearly, the downregulation of USP39 greatly promoted ZEB1 ubiquitination in HepG2 and SK-hep-1 cells (Fig. 3F)."
USP39 inhibits ZEB1.
| 2
USP39 inhibits ZEB1. 2 / 2
| 2

reach
"The zinc finger E-box binding homology cassette (ZEB1) is a key inducer of epithelial–mesenchymal transition (EMT), promoting cancer cell metastasis; USP39 inhibits the degradation of ZEB1 and promotes the development of EMT through deubiquitylation, further accelerating the invasion and metastasis of HCC cells [38]."

reach
"Collectively, we believe that USP39 reduces the degradation of ZEB1 protein through direct deubiquitination, which promotes EMT progression and the development of HCC.Ubiquitination and deubiquitination are two contrasting posttranslational processes that involve in the conjugation and removing of ubiquitin from targeted proteins, respectively."
USP39 activates ZEB1.
| 2
USP39 activates ZEB1. 2 / 2
| 2

reach
"Moreover, USP39 depletion inhibits HCC cell proliferation and metastasis by promoting ZEB1 degradation."

reach
"The results indicated that USP39 overexpression largely increased the half-life of the ZEB1 protein in HepG2 cells (Fig. 3D)."
USP39 affects FOXM1
3 | 13 8
USP39 binds FOXM1.
3 | 3 8
3 | 3 8

No evidence text available

sparser
"Additionally, the deubiquitinating enzyme USP39 can also directly bind to FOXM1 and further deubiquitinate and stabilize FOXM1."

sparser
"In our work, USP39 interacted with FOXM1 and promoted the splicing of FOXM1 pre-mRNA."

No evidence text available

No evidence text available

reach
"Additionally, the deubiquitinating enzyme USP39 can also directly bind to FOXM1 and further deubiquitinate and stabilize FOXM1."

reach
"We also used RIP assay to confirm that FOXM1 bound with USP39 in human CSCC tissue (Additional file 1: Fig S2B)."

sparser
"The interaction between USP39 and FOXM1 was investigated using co-immunoprecipitation (co-IP) and in vitro deubiquitination analysis."

sparser
"It is worth noting that, as in HCC, USP39 interacts with FOXM1 in BC regulating ubiquitination and stabilizing FOXM1 through competitive bonding with the E3 ubiquitin ligase APC/Cdh1, which regulates BC cell proliferation ( xref )."

sparser
"In general, our research revealed the USP39-FOXM1 axis as a critical driver of breast cancer cell proliferation and provided a theoretical foundation for targeting the USP39-FOXM1 axis for pancreatic cancer treatment."
USP39 activates FOXM1.
| 4
USP39 activates FOXM1. 4 / 4
| 4

reach
"Mechanistically, USP39 was revealed to upregulate SIRT7 by promoting the transcriptional activity of FOXM1."

reach
"The results suggest that knockdown of USP39 inhibits the growth of HCC in vitro and in vivo, potentially through the induction of G2/M arrest by regulating the pre-mRNA splicing of FoxM1."

reach
"Inhibition of USP39 by siRNA has downregulated FOXM1 and in turn led to tumor volume reduction in xenograft model of HCC."

reach
"In our work, USP39 interacted with FOXM1 and promoted the splicing of FOXM1 pre-mRNA."
USP39 increases the amount of FOXM1.
| 3
USP39 increases the amount of FOXM1. 3 / 3
| 3

reach
"USP39 promotes breast cancer proliferation by regulating FOXM1 levels via deubiquitination [39]."

reach
"USP39 silencing also caused significant decrease in FOXM1 protein expression in CSCC cells."

reach
"SIRT7 promotes USP39 protein stability via deacetylation at the site K428, and USP39 facilitates the splicing efficacy of FOXM1 to elevate FOXM1 expression."
USP39 inhibits FOXM1.
| 1
USP39 inhibits FOXM1. 1 / 1
| 1

reach
"This data was further confirmed by western blot analysis that showed a significant downregulation of FOXM1 induced by USP39 knockdown in CSCC cells (Fig. 5C)."
USP39 deubiquitinates FOXM1.
| 1
USP39 deubiquitinates FOXM1. 1 / 1
| 1

reach
"Additionally, the deubiquitinating enzyme USP39 can also directly bind to FOXM1 and further deubiquitinate and stabilize FOXM1."
USP39 decreases the amount of FOXM1.
| 1
USP39 decreases the amount of FOXM1. 1 / 1
| 1

reach
"It was observed that unspliced FOXM1 transcript expression was significantly upregulated by USP39 knockdown, while the expression of spliced FOXM1 exhibited a significant decrease after silencing USP39 (Fig. 5D)."
MYC affects USP39
1 | 1 5 17
MYC binds USP39.
1 | 16
1 | 16

sparser
"Finally, Boyden chamber assays demonstrated that OPM2 and U266 cells overexpressing either the GFP-USP39 or Myc-USP39 form exhibited enhanced migratory capacity."

sparser
"Injection of OPM2 cells stably overexpressing USP39 (Myc-USP39) or control cells (Myc) into the perivitelline space of zebrafish larvae allowed for real time visualization of local and distant metastatic events using fluorescence microscopy after 2 days."

sparser
"Moreover, an in vitro deubiquitination assay designed by mixing USP39-Myc or USP14-Myc with E-HA, which was purified from cells transfected with USP-Myc using anti-Myc beads or cells transfected with [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"We next constructed a series of expression vectors encoding Cyclin B1 mutants in which lysine (K) residues that might be ubiquitinated were replaced with arginine (R), then assessed their ubiquitination levels affected by Myc-USP39 in HEK293T cells."

sparser
"Among the Cyclin B1 mutants we constructed, only the ubiquitination of K242R mutant was not reduced by the Myc-USP39 ( xref h)."

sparser
"USP39 or USP14 was immunoprecipitated from HEK293T cells overexpressing USP39-Myc or USP14-Myc, using anti-Myc antibody plus protein G agarose beads."

No evidence text available

sparser
"USP39-Myc failed to co-immunoprecipitation mutant E with a deletion of amino acids 11–26 ( Fig. 4 F) which located in the first helix of the E protein ( Fig. 4 E), and showed weaker interaction with E[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Transfection of a plasmid encoding an exogenous form of USP39 (Myc-USP39) alone did not affect cellular metabolism."

sparser
"However, co-transfection of USP39 siRNA and Myc-USP39 plasmid led to a partial rescue of the decline in cellular metabolism, thus demonstrating the specificity of the observed effects to USP39 modulation (Fig.  xref E)."
MYC activates USP39.
| 1 2 1
MYC activates USP39. 4 / 4
| 1 2 1

sparser
"Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells."

eidos
"In contrast , inhibition of c-MYC by shRNA decreased USP39 expression ( Fig. 4A-B ) ."

reach
"The effect of c-MYC on USP39 expression was further investigated by performing a luciferase assay, and the result showed that forced expression of c-MYC increased luciferase activity of the USP39 promoter reporter containing the wild-type but not the mutant c-MYC binding site."

reach
"Furthermore, the loss of Usp39 dramatically delays Myc-driven B cell lymphomagenesis, highlighting Usp39 as a potential therapeutic target for B cell malignancies.To infer the stages in which Usp39 mi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
MYC increases the amount of USP39.
| 3
MYC increases the amount of USP39. 3 / 3
| 3

reach
"C-MYC activates the transcription of USP39 in ovarian cancer cells."

reach
"As expected, overexpression of c-MYC significantly increased USP39 expression at both the RNA and protein level."

reach
"In contrast, inhibition of c-MYC by shRNA decreased USP39 expression."
USP39 affects TRIM26
3 | 13 3
USP39 binds TRIM26.
3 | 5 3
3 | 5 3

sparser
"Intriguingly, USP39 can bind to TRIM26, suggesting that TRIM26 and USP39 governed the balance of ZEB1 expression levels and determined the fate of HCC cells on proliferation and metastasis [153] ."

reach
"More importantly, RNA immunoprecipitation showed that USP39 is bound to TRIM26 mRNA."

No evidence text available

No evidence text available

reach
"Intriguingly, USP39 can bind to TRIM26, suggesting that TRIM26 and USP39 governed the balance of ZEB1 expression levels and determined the fate of HCC cells on proliferation and metastasis [153] ."

No evidence text available

sparser
"USP39 and TRIM26 bind to each other directly and maintain the ubiquitin level of ZEB1, thus determining the proliferation and migration of HCC ( xref )."

sparser
"Additionally, USP39 directly interacts with the E3 ligase TRIM26, which is underexpressed in human HCC tissues, and can inhibit the proliferation and migration of HCC cells."

reach
"In addition, a direct interaction between USP39 and TRIM26 was identified by co-immunoprecipitation and immunofluorescence staining assays, respectively."

reach
"Co-immunoprecipitation assays showed a direct interaction between endogenous USP39 and TRIM26 in SK-hep-1 cells (Fig. 4A)."
USP39 inhibits TRIM26.
| 5
USP39 inhibits TRIM26. 5 / 5
| 5

reach
"Using two pairs of primers, one for alternative splicing and the other for constitutive splicing of the TRIM26 mRNA, we confirmed that knockdown of USP39 increased alternative splicing of TRIM26 mRNA whereas constitutive splicing did not (Fig. 5F)."

reach
"Moreover, overexpression of USP39 reduced the alternative splicing of TRIM26 mRNA with no effect on the constitutive splicing (Fig.5G)."

reach
"We confirmed that USP39 deletion increased the alternate splicing transcript of TRIM26 without significant changes in its constitutive splicing."

reach
"USP39 suppressed the shearing and maturation of TRIM26 precursor mRNA, as demonstrated by immunoprecipitation experiments indicating a direct interaction between the two."

reach
"We hypothesized that USP39 antagonizes TRIM26 in targeting ZEB1 for ubiquitin-dependent proteasomal degradation, to regulate the proliferation and migration of HCC cells."
USP39 decreases the amount of TRIM26.
| 3
USP39 decreases the amount of TRIM26. 3 / 3
| 3

reach
"These data demonstrate that USP39 regulates TRIM26 pre-mRNA splicing and maturation, and led to decrease of TRIM26 protein level at least in part by suppressing splicing of its pre-mRNA."

reach
"We first examined the effect of USP39 on the levels of TRIM26 mRNA by using qRT-PCR, discovering that knockdown of USP39 increased transcript level of TRIM26."

reach
"Although our previous study found that knockdown of USP39 could increase the protein level of TRIM26, no further exploration was performed to the mechanism of USP39 regulating TRIM26."
USP39 affects SIRT7
6 | 7 6
USP39 binds SIRT7.
6 | 2 6
6 | 2 6

sparser
"Moreover, Dong et al.’s study revealed that USP39 interacts with SIRT7, which deacetylates USP39 to enhance its stability, thereby further promoting HCC development ( xref )."

No evidence text available

No evidence text available

No evidence text available

sparser
"The results of Co-IP revealed that Flag-USP39 was significantly enriched in the precipitates of Myc-SIRT7 and vice versa, which indicated that USP39 interacted with SIRT7 in CaSki and SiHa cells (Fig.  xref B)."

No evidence text available

No evidence text available

reach
"The binding between USP39 and SIRT7 was evaluated by western blot using anti-Flag tag (ab205606, 1/3000, abcam) or anti-Myc (ab32, 1/3000, abcam) antibodies."

sparser
"In addition, we also evaluated the interaction between SIRT7 and USP39 in human CSCC tissues."

sparser
"Co-immunoprecipitation indicated that SIRT7 interacted with USP39 (Additional file xref : Fig S2A)."
USP39 increases the amount of SIRT7.
| 4
USP39 increases the amount of SIRT7. 4 / 4
| 4

reach
"These results suggested that USP39 promoted the transcriptional activity of FOXM1 to promote SIRT7 transcription."

reach
"USP39 promotes SIRT7 expression by activating the transcriptional activity of FOXM1."

reach
"Taken together, these results indicate that USP39 promotes SIRT7 transcription by elevating the transcriptional activity of FOXM1."

reach
"USP39 was deacetylated by SIRT7 and promoted SIRT7 expression by facilitating FOXM1-mediated SIRT7 transcription."
USP39 activates SIRT7.
| 1
USP39 activates SIRT7. 1 / 1
| 1

reach
"Mechanistically, USP39 was revealed to upregulate SIRT7 by promoting the transcriptional activity of FOXM1."
| 1 18
| 15

reach
"USP39 protein promotes the growth and metastasis of colorectal cancer mainly through the Wnt/β-catenin pathway [8] ."

reach
"Thus, depletion of USP39 could inhibit the proliferation and metastasis of HCC cells."

reach
"Knockout of USP39 can inhibit tumor genesis, induce cell apoptosis, and inhibit lung adenocarcinoma cell metastasis [13]."

reach
"For instance, USP39 promotes colorectal cancer growth and metastasis through the Wnt and beta-catenin pathway [XREF_BIBR]."

reach
"Indeed, silencing USP39 expression markedly inhibited the proliferation and metastasis of HCC cells in vitro and in vivo experiments, indicating the potential carcinogenic effect of USP39 in HCC development."

reach
"For example, Yuan et al. [13] found that USP39 is upregulated in NSCLC tissues, and USP39 knockout can inhibit the growth and metastasis of NSCLC cells."

reach
"Deubiquitinating enzyme USP39 promotes the growth and metastasis of gastric cancer cells by modulating the degradation of RNA-binding protein RBM39."

reach
"The depletion of USP39 could inhibit the proliferation and metastasis of HCC cells [11]."

reach
"The results showed that USP39 knockdown led to an obvious reduction in tumor metastasis, while TRIM26 downregulation enhanced the tumor metastasis and reversed the reduction of shUSP39-related cell metastasis and the number of nodules in the lung (Fig. 8G, H)."

reach
"USP39 contributes to CRC growth and metastasis through the Wnt/β-catenin pathway."
| 1 3

reach
"Gan et al. demonstrated that USP39 expression was overexpressed in osteosarcoma and that USP39 knockdown arrested osteosarcoma cells in G2/M phase, thereby inhibiting tumor growth and metastasis (104)."

trips
"Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway."

reach
"Previous studies have reported that USP39 silencing inhibits colon cancer cell growth and metastasis, and induces apoptosis by regulating the Wnt/β-catenin signaling pathway [31]."

reach
"USP39 deficiency activates p53 pathway–induced apoptosis and metastasis in NSCLC [25]."
USP39 affects CHEK2
4 1 | 3 11
USP39 binds CHEK2.
4 | 11
4 | 11

sparser
"Additionally, endogenous immunoprecipitation further confirmed that USP39 binds to CHK2 ( Fig. 2 C and D)."

sparser
"Hence, we next examined whether the interaction of USP39 and CHK2 was mediated by DNA damage."

sparser
"In addition, the binding of USP39 and CHK2 didn't change upon Lambda protein phosphatase (λPP) treatment ( Fig. 2 G), suggesting that the interaction between USP39 and CHK2 is independence of DNA dama[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Taken together, our findings suggest that USP39 interacts with CHK2."

sparser
"Since USP39-CHK2 axis regulates cell cycle checkpoint and apoptosis, we next examined the expression of Ki67 and cleaved caspase 3 in these cancer samples."

sparser
"Furthermore, our data shown USP39-CHK2 axis playing an important role in regulation of apoptosis and cell cycle checkpoint induced by DNA damage."

sparser
"Hence, we next examined whether USP39-CHK2 axis affects lung cancer cells response to chemotherapy and radiation."

No evidence text available

sparser
"Thus, we also examined the roles of USP39-CHK2 axis in chemo-radiation response."

sparser
"Hence, our findings suggest that USP39-CHK2 axis may function as the potential biomarker for predicting chemo-radiation response in lung cancer."
USP39 deubiquitinates CHEK2.
1 | 2
USP39 deubiquitinates CHEK2. 3 / 3
1 | 2

reach
"Additionally, USP39 deubiquitinates and stabilizes CHK2 in lung cancer, and the knockdown of USP39 compromises G2/M checkpoint, thereby conferring decreased apoptosis and resistance to chemotherapy and radiotherapy [114]."

reach
"Mechanistically, USP39 deubiquitinates and stabilizes CHK2, which in turn enhances CHK2 stability."

"Mechanistically, <span class="match term0">USP39</span> deubiquitinates and stabilizes <span class="match term1">CHK2</span>, which in turn enhances <span class="match term1">CHK2</span> stability"
USP39 decreases the amount of CHEK2.
| 1
USP39 decreases the amount of CHEK2. 1 / 1
| 1

reach
"USP39 directly deubiquitinates checkpoint kinase 2 (CHK2) to stabilize its expression, while the knockdown of USP39 significantly reduces CHK2 expression."
CCNB1 affects USP39
5 | 3 11
5 | 3 11

sparser
"Our findings suggest that USP39-Cyclin B1 axis may function as the potential therapeutic target for the treatment of human glioma."

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"Co-immunoprecipitation and other assays were performed to detect the interacting of Cyclin B1 and USP39."

reach
"Next, we sought to detect an interaction of Cyclin B1 and USP39."

reach
"Additionally, the interaction between endogenous USP39 and Cyclin B1 in U87 cells was demonstrated by anti-Cyclin B1 immunoprecipitation (Fig. 2e)."

sparser
"USP39 interacts with Cyclin B1 and stabilizes its expression by deubiquitinating Cyclin B1."
USP39 affects TP53
1 | 1 12 3
USP39 inhibits TP53.
| 1 8
USP39 inhibits TP53. 9 / 9
| 1 8

eidos
"Further studies demonstrated that depletion of USP39 results in an upregulation of p53 through prolonging its half-life and activating its transcriptional activation activity ."

reach
"Furthermore, USP39 knockdown increased the stability of the p53 protein by prolonging its half-life."

reach
"on A549 cells to confirm the key role of p53, the WB result demonstrated that exposure to PFT-alpha (30 or 40 mum/48 h) clearly inhibited the p53 pathway activation, which activated by USP39 knockdown in A549 cells."

reach
"USP39 deficiency activates p53 pathway–induced apoptosis and metastasis in NSCLC [25]."

reach
"Moreover, depletion of USP39 blocked activation of Akt, mTOR, p53, and PARP signaling pathways."

reach
"USP39 attenuates the antitumor activity of cisplatin on colon cancer cells dependent on p53."

reach
"USP39 down-regulates the p53/p21 signaling pathway and stabilizes CDK1 and cyclin B1 to promote the proliferation of ovarian cancer cells [34]."

reach
"Meanwhile, we found that USP39 knockdown also activates the p53 pathway, upregulation of p53, p-p53 (S15), p21 and BAX in HCC827 cells."

reach
"Altogether, these results suggest that USP39 knockdown causes a significant accumulation of p53 via regulating both transcriptional levels and post-translational modifications of p53."
USP39 binds TP53.
1 | 2 3
1 | 2 3

sparser
"USP39 indirectly regulates MDM2 or directly binds to p53, affecting its stability and transcriptional activity, and inhibiting tumor suppressive function [ xref ]."

reach
"Given the importance of the p53 pathway in the tumor promotor function of USP39, further investigations should address these key questions : (1) How does USP39 regulate p53 and what is the interaction between USP39 and p53?"

sparser
"Given the importance of the p53 pathway in the tumor promotor function of USP39, further investigations should address these key questions: (1) How does USP39 regulate p53 and what is the interaction between USP39 and p53? (2) is the oncogenic function of USP39 solely dependent on the p53 pathway, or is another signaling pathway involved?"

No evidence text available

reach
"In osteosarcoma cells under ER stress, P53 directly binds to the promoter of miR-1281, and down-regulates USP39 in osteosarcoma cells through the p5-Mir-1281-USP39 axis, an ERS response pathway, to inhibit and promote cell apoptosis [111]."

sparser
"ERS-induced miR-1281, whose promoter binds to p53 and targets USP39, facilitating the apoptosis of osteosarcoma cells xref ."
USP39 activates TP53.
| 2
USP39 activates TP53. 2 / 3
| 2

reach
"The underlying mechanism is demonstrated by knocking down USP39, that results in p53 upregulation, associated with its prolonged half-life."

reach
"In addition, by employing a double luciferase reporter system assay, we found that depletion of USP39 enhances p53 responsive transcriptional reporter activity."
USP39 affects GRHL3
| 6 12
USP39 binds GRHL3.
| 4 12
| 4 12

sparser
"These findings further support the idea that endogenous USP39 might bind GRHL3 in living cells."

sparser
"To test the interaction between GRHL3 and USP39 within MCF7 cells under physiological conditions, we immunoprecipitated protein complexes in cell extracts using an antibody against GRHL3."

sparser
"To verify the interaction between USP39 and GRHL3 proteins, a visible immunoprecipitation (VIP) assay, a simple method to examine the interaction between two proteins without respective antibodies, was performed (Fig. S xref ) xref ."

sparser
"This finding suggests the possible interaction between GRHL3 and USP39 in vitro."

sparser
"To map which protein domains are responsible for the interaction between GRHL3 and USP39, we generated two series of constructs consisting of three domains of Grhl3 cDNA and two domains of Usp39 cDNA fused to GST , respectively, and examined binding activity to each other (Fig. S xref )."

sparser
"These biochemical studies demonstrate that over-expressed GRHL3 can interact with USP39 via the CP2/Ub-like domains of GRHL3, and the ZnF domain of USP39."

sparser
"These aforementioned findings, together with biochemical results, suggest that over-expressed USP39 interacts with GRHL3 in the cytoplasm mainly through the Ub-like domain of GRHL3."

sparser
"To evaluate the genetic interaction between Grhl3 and Usp39 , we analyzed phenotypes of epidermal development during eyelid closure since Grhl3 −/− embryos have been reported to be defective in eyelid closure with a low penetrance (Figs.  xref and S xref ) xref , xref ."

sparser
"To explore the exact timing and place of GRHL3 interaction with the USP39 protein in epidermal cells, we analyzed expression of the two genes and eyelid phenotypes more closely (Fig.  xref )."

sparser
"To determine when Grhl3 interacts with Usp39 during eyelid closure, we examined Grhl3 and Usp39 expression at the mRNA level in sections, and at the protein level in whole-mount of wild-type embryos at E15.5 (Figs.  xref and S xref )."
USP39 activates GRHL3.
| 2
USP39 activates GRHL3. 2 / 2
| 2

reach
"Therefore, we propose that USP39 can activate non-canonical Wnt signaling partly by allowing GRHL3 to localize in the cytoplasm.This study demonstrates that Usp39 and Grhl3 cooperate to contribute to epithelial morphogenesis during mouse eyelid closure (Figs."

reach
"Considering that USP39 mediates the cytoplasmic localization of GRHL3, it can be assumed that USP39 expression would be observed during epidermal maturation."
USP39 affects MYC
1 | 16
1 | 16

sparser
"Finally, Boyden chamber assays demonstrated that OPM2 and U266 cells overexpressing either the GFP-USP39 or Myc-USP39 form exhibited enhanced migratory capacity."

sparser
"Injection of OPM2 cells stably overexpressing USP39 (Myc-USP39) or control cells (Myc) into the perivitelline space of zebrafish larvae allowed for real time visualization of local and distant metastatic events using fluorescence microscopy after 2 days."

sparser
"Moreover, an in vitro deubiquitination assay designed by mixing USP39-Myc or USP14-Myc with E-HA, which was purified from cells transfected with USP-Myc using anti-Myc beads or cells transfected with [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"We next constructed a series of expression vectors encoding Cyclin B1 mutants in which lysine (K) residues that might be ubiquitinated were replaced with arginine (R), then assessed their ubiquitination levels affected by Myc-USP39 in HEK293T cells."

sparser
"Among the Cyclin B1 mutants we constructed, only the ubiquitination of K242R mutant was not reduced by the Myc-USP39 ( xref h)."

sparser
"USP39 or USP14 was immunoprecipitated from HEK293T cells overexpressing USP39-Myc or USP14-Myc, using anti-Myc antibody plus protein G agarose beads."

No evidence text available

sparser
"USP39-Myc failed to co-immunoprecipitation mutant E with a deletion of amino acids 11–26 ( Fig. 4 F) which located in the first helix of the E protein ( Fig. 4 E), and showed weaker interaction with E[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Transfection of a plasmid encoding an exogenous form of USP39 (Myc-USP39) alone did not affect cellular metabolism."

sparser
"However, co-transfection of USP39 siRNA and Myc-USP39 plasmid led to a partial rescue of the decline in cellular metabolism, thus demonstrating the specificity of the observed effects to USP39 modulation (Fig.  xref E)."
USP39 affects CTNNB1
2 | 11 3
USP39 binds CTNNB1.
2 | 3
2 | 3

sparser
"Co-immunoprecipitation and ubiquitination assays were performed to confirm the interaction between USP39 and β-catenin."

sparser
"These observations suggested that deubiquitinase USP39 interacts with β-catenin to inhibit the HCC cell proliferation."

No evidence text available

sparser
"Next, to exclude the possibility of any involvement of USP39 in canonical Wnt signaling, we tested for any genetic interaction between β-catenin and Usp39 (Fig. S xref )."

No evidence text available
USP39 increases the amount of CTNNB1.
| 4
USP39 increases the amount of CTNNB1. 4 / 4
| 4

reach
"Detecting proteins separated from cytoplasmic and nuclear by western blotting showed that, knockdown of USP39 induced a reduction of nuclear β-catenin (Fig. 2F), whereas USP39 overexpression increased β-catenin level in the nucleus (Fig. 2G)."

reach
"In summary, our data reveal a novel mechanism in the progress of HCC that USP39 promotes the proliferation and migration of HCC through increasing beta-catenin level via both direct deubiquitination and reducing TRIM26 pre-mRNA maturation and splicing, which may provide a new idea and target for clinical treatment of HCC."

reach
"Furthermore, overexpression of USP39 increased β-catenin protein level, but co-overexpression of USP39 and TRIM26 counteracted the increase (Fig. 4B)."

reach
"In contrast, western blotting revealed that knockdown of USP39 led to a reduction of β-catenin (Fig. 2C), and overexpression of USP39 increased β-catenin protein level (Fig. 2D) in HCC cells."
USP39 deubiquitinates CTNNB1.
| 4
USP39 deubiquitinates CTNNB1. 4 / 4
| 4

reach
"On account of the fact that β-catenin protein level was decreased with no change on mRNA level, and USP39 is a deubiquitinating enzyme, we hypothesized whether USP39 de-ubiquitinate and stabilize β-catenin."

reach
"Altogether, these data strongly supported that USP39 deubiquitinates β-catenin, and suppressed TRIM26 pre-mRNA maturation, further influenced its protein level and decreased its ubiquitination to β-catenin, which plays a key role in promoting HCC progression."

reach
"Furthermore, immunoprecipitation demonstrated that USP39 reduced the ubiquitination of β-catenin in SK-hep-1 cells (Fig. 3D)."

reach
"GST pull-down assay further demonstrated that USP39 could deubiquitylate β-catenin in vitro (Fig. 3E)."
USP39 activates CTNNB1.
| 3
USP39 activates CTNNB1. 3 / 4
| 3

reach
"Double knockdown of TRIM26 and USP39 eliminated the reduction of β-catenin caused by USP39 silencing."

reach
"Here, we prove that USP39 promotes HCC cell proliferation and migration by directly deubiquitin beta-catenin, a key molecular of Wnt/beta-catenin signaling pathway whose abnormal expression or activation results in several tumors, following its co-localization with USP39."

reach
"In detail, on one hand, USP39 decreases β-catenin degradation through its deubiquitination function to promote HCC progression."
USP39 affects cell growth
| 15 1
USP39 activates cell growth.
| 10
| 10

reach
"In melanoma, knockdown USP39 inhibited cell growth and induced cell cycle arrest and apoptosis."

reach
"In conclusion, the inhibition of USP39 in CAL27 cells suppressed cell growth probably via induction cell cycle arrest and apoptosis."

reach
"In conclusion, knockdown of USP39 by RNAi inhibited cell growth due to inactivation of the CDK1 and CyclinB complex."

reach
"Previous studies have reported that USP39 silencing inhibits colon cancer cell growth and metastasis, and induces apoptosis by regulating the Wnt/β-catenin signaling pathway [31]."

reach
"These findings are in agreement with cell growth inhibition, which suggest that USP39 could modulate osteosarcoma cell growth via cell cycle control."

reach
"And knocking-down of USP39 and co-expression of SP1 significantly induced cell growth and proliferation compared with knocking-down of USP39 only."

reach
"USP39 knockdown inhibits cell growth and enhances cell apoptosis."

reach
"Our results suggest that USP39 condensates correlated with the expression of GLI1 and contributed to lung cancer progression by promoting cell growth and migration (Fig. 8)."

reach
"In osteosarcoma cells, a decreased USP39 expression inhibited cell growth and induced apoptosis."

reach
"Lung cancer cell growth and migration were dramatically inhibited by USP39 knockdown, which was rescued by exogenous USP39 complementation."
USP39 inhibits cell growth.
| 5 1
| 5 1

reach
"USP39 knockdown inhibited cell proliferation and colony formation in vitro in the HepG2 cells, while upregulation of USP39 promoted tumor cell growth."

reach
"Depletion of USP39 by siRNA significantly suppressed cell growth and decreased invasive capacity of RCC cells."

reach
"Downregulation of USP39 significantly inhibited cell growth and migration in lung adenocarcinoma cells, while the inhibitory effects were rescued by restoration of USP39 expression."

reach
"Recently, scientists reported aberrant USP39 expression could inhibit breast cancer cell growth in vitro [XREF_BIBR], however, little is known about how USP39 functions in human osteosarcoma and whether it can be used as an potential therapeutic target."

reach
"Previous studies found that down-regulation of USP39 could inhibit cell growth and colony formation of human breast cancer cells [XREF_BIBR]."

sparser
"In melanoma, knockdown USP39 inhibited cell growth and induced cell cycle arrest and apoptosis ( xref )."
USP39 affects SP1
3 | 5 8
USP39 binds SP1.
3 | 8
3 | 8

sparser
"Then, we used nude mice to establish a cancer xenograft model to demonstrate that the function of USP39-SP1 axis in tumor growth."

sparser
"Miyamoto-Sato's study found that USP39 and SP1 protein may interact with each other in a dataset of protein-protein interactions (PPIs) network [14] ."

sparser
"This provides an effective anti-tumor therapeutic strategy of HCC by an understanding of the USP39-SP1 protein axis."

sparser
"Next, we extended our analysis by investigating whether endogenous USP39 and SP1 can interact with each other."

sparser
"Together, these results suggest that USP39 directly interacts with SP1 protein."

sparser
"Co-IP assay was used to test the binding of the full-length USP39 and SP1 (wildtype) and the deletion mutants in 293 T cells."

sparser
"SP1 binds to C-terminal domain (amino acids 200–565) of USP39 (Supplementary Material Fig. 1 B)."

No evidence text available

sparser
"Interaction of USP39 and SP1 plays an important role in promoting cell proliferation, cell cycle, and tumor growth of HCC."

No evidence text available
USP39 deubiquitinates SP1.
| 3
USP39 deubiquitinates SP1. 3 / 3
| 3

reach
"In addition, USP39 participates in the deubiquitination of SP1 protein and promotes the proliferation of HCC cells in a SP1-dependent manner (26)."

reach
"Since USP39 is a de-ubiquitinating enzyme, we explored whether USP39 de-ubiquitinates and stabilizes SP1 protein."

reach
"For example, USP39 promotes the tumorigenesis of hepatocellular carcinoma by stabilizing and deubiquitinating SP1 ."
USP39 increases the amount of SP1.
| 1
USP39 increases the amount of SP1. 1 / 1
| 1

reach
"As shown in Fig. 5 A , ectopic expression of USP39 WT, but not USP39 CA construct, can increase the exogenous SP1 protein expression in a dose-dependent manner, demonstrating that the de-ubiquitinase [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 activates SP1.
| 1
USP39 activates SP1. 1 / 1
| 1

reach
"Thereby, we further explored whether USP39 can promote SP1 stabilization through the regulation of SP1 de-ubiquitination."
GRHL3 affects USP39
| 4 12
| 4 12

sparser
"These findings further support the idea that endogenous USP39 might bind GRHL3 in living cells."

sparser
"To test the interaction between GRHL3 and USP39 within MCF7 cells under physiological conditions, we immunoprecipitated protein complexes in cell extracts using an antibody against GRHL3."

sparser
"To verify the interaction between USP39 and GRHL3 proteins, a visible immunoprecipitation (VIP) assay, a simple method to examine the interaction between two proteins without respective antibodies, was performed (Fig. S xref ) xref ."

sparser
"This finding suggests the possible interaction between GRHL3 and USP39 in vitro."

sparser
"To map which protein domains are responsible for the interaction between GRHL3 and USP39, we generated two series of constructs consisting of three domains of Grhl3 cDNA and two domains of Usp39 cDNA fused to GST , respectively, and examined binding activity to each other (Fig. S xref )."

sparser
"These biochemical studies demonstrate that over-expressed GRHL3 can interact with USP39 via the CP2/Ub-like domains of GRHL3, and the ZnF domain of USP39."

sparser
"These aforementioned findings, together with biochemical results, suggest that over-expressed USP39 interacts with GRHL3 in the cytoplasm mainly through the Ub-like domain of GRHL3."

sparser
"To evaluate the genetic interaction between Grhl3 and Usp39 , we analyzed phenotypes of epidermal development during eyelid closure since Grhl3 −/− embryos have been reported to be defective in eyelid closure with a low penetrance (Figs.  xref and S xref ) xref , xref ."

sparser
"To explore the exact timing and place of GRHL3 interaction with the USP39 protein in epidermal cells, we analyzed expression of the two genes and eyelid phenotypes more closely (Fig.  xref )."

sparser
"To determine when Grhl3 interacts with Usp39 during eyelid closure, we examined Grhl3 and Usp39 expression at the mRNA level in sections, and at the protein level in whole-mount of wild-type embryos at E15.5 (Figs.  xref and S xref )."
USP39 affects EGFR
| 10 1
USP39 activates EGFR.
| 5
USP39 activates EGFR. 5 / 7
| 5

reach
"It was found in our previous study that USP39 knockdown could inhibit the abnormal proliferation of prostate cancer cells by inhibiting the splicing maturation and transcriptional prolongation of EGFR mRNA [16]."

reach
"To verify whether the regulatory effect of USP39 was EGFR specific, ectopic expression of USP39 were performed in PC-3 and DU145 cells, which showed that overexpressed USP39 upregulated EGFR mRNA and protein levels, indicating that EGFR is a downstream target of USP39."

reach
"USP39 is positively correlated with EGFR (epidermal growth factor receptor) levels; USP39 upregulates the mRNA and protein expression levels of EGFR (Huang et al., 2016)."

reach
"We hypothesized that USP39 could up-regulate EGFR by increasing the pre-mRNA splicing."

reach
"The results demonstrated that the level of the 3 '-end of EGFR decreased (P = 0.0015) more sharply than that of the 5 '-end (P = 0.0069), and the ratio ofthe 3 '-end to 5 '-end levels was significant decreased (P = 0.0297), implying that knockdown of USP39 might inhibit the transcription elongation of EGFR, and might produce unstable EGFR mRNA fragments lacking the 3 '-UTR."
USP39 increases the amount of EGFR.
| 3
USP39 increases the amount of EGFR. 3 / 4
| 3

reach
"Silencing of USP39 inhibited the expression of EGFR 3 '-end, and presented a remarkable block to the maturation of EGFR mRNA, suggesting that silencing of USP39 decreased the transcriptional elongation and maturation of EGFR mRNA."

reach
"Microarray analysis suggested that knockdown of USP39 caused a reduced expression of EGFR."

reach
"In prostate cancer, USP39 promotes cell proliferation by modulating mutations at the K6, K16, K29, K51, and K73 loci of SUMO and regulating EGFR mRNA transcription [47, 91]."
USP39 phosphorylates EGFR.
| 1 1
USP39 leads to the phosphorylation of EGFR. 2 / 2
| 1 1

reach
"Mechanistic analyses indicate that USP39 promotes the phosphorylation of AKT, EGFR, and cyclin B1, while it deters the activation of PARP and Caspase-3, thereby enhancing cell proliferation, migration, and invasion, and curbing apoptosis [78]."

sparser
"Mechanistic analyses indicate that USP39 promotes the phosphorylation of AKT, EGFR, and cyclin B1, while it deters the activation of PARP and Caspase-3, thereby enhancing cell proliferation, migration, and invasion, and curbing apoptosis [ xref ]."
USP39 decreases the amount of EGFR.
| 1
USP39 decreases the amount of EGFR. 1 / 2
| 1

reach
"Knockdown of USP39 downregulated EGFR expression in PC-3 and DU145 cells in mRNA (P < 0.0001 and P < 0.0001, respectively) and protein levels."
Histone affects USP39
| 13 2
Histone binds USP39.
| 7 2
| 7 2

reach
"These results indicate that the interaction between Sad1 and histones is required for the distribution of Sad1 in the nuclear envelope but not for its localization to the SPB."

reach
"We next investigated whether the interaction between Sad1 and histones is important for the centromere-NE association."

reach
"These data indicate that the interaction between Sad1 and histone is not involved in centromere clustering at SPB, which is consistent with the previous finding that Sad1 is essential for linking centromeres with SPB ."

sparser
"To further examine whether histone could bind to the USP39 promoter active region in vitro, an EMSA was conducted."

reach
"These results indicated that histone indeed bound to the predicted promoter active region binding site of USP39 in vitro."

reach
"We hypothesize that these nuclear membrane proteins may form a synergistic network to create a microenvironment to benefit heterochromatin organization and maintenance at the nuclear periphery, which requires further investigation.Fission yeast Sad1 binds both canonical histone H2A-H2B and histone variant H2A.Z-H2B, whereas the budding yeast SUN-family protein, Mps3, specifically recognizes H2A.Z ."

sparser
"These results indicated that histone indeed bound to the predicted promoter active region binding site of USP39 in vitro."

reach
"To examine the effect of 5 R mutation on the interaction between Sad1 and histone in vivo, we created a stain carrying Sad1-5R-HA and H2B -FLAG and conducted Co-IP experiments."

reach
"8b, c), indicating that Sad1 associates with heterochromatin regions.Next, we wanted to test whether the histone binding activity of Sad1 is important for heterochromatin silencing."
Histone increases the amount of USP39.
| 5
Histone increases the amount of USP39. 5 / 5
| 5

reach
"Wei et al. observed significantly increased Kla in endometrial cancer tissues, where histone Kla enhances USP39 expression, driving the PI3K/AKT/HIF-1α pathway to promote malignancy 162."

reach
"Mechanically, histone lactylation stimulated USP39 expression to promote tumor progression."

reach
"Histone lactylation promotes malignant progression by facilitating USP39 expression to target PI3K/AKT/HIF-1alpha signal pathway in endometrial carcinoma."

reach
"In addition, histone lactylation promotes malignant progression by promoting the expression of ubiquitin specific peptidase 39 (USP39) targeting the PI3K/AKT/HIF-1α signaling pathway in endometrial cancer (Wei et al., 2024)."

reach
"Mechanistically, histone lactylation promoted the expression of ubiquitin-specific peptidase 39 (USP39), which interacted with, stabilized, and de-ubiquitinated phosphoglycerate kinase 1 (PGK1), thereby activating the PI3K/AKT/HIF-1α signaling pathway."
Histone activates USP39.
| 1
Histone activates USP39. 1 / 1
| 1

reach
"Thus, Sad1 can undergo liquid-liquid phase separation in vitro and in vivo, and histone H2A-H2B enhances the phase separation ability of Sad1."
ETS2 affects USP39
| 6 9
| 6 9

sparser
"Strategies that promote the interaction between USP39 and ETS2 may offer new avenues for precise therapeutic interventions."

sparser
"Additionally, USP39 can interact with ETS2 via its N-terminal region, thereby regulating the transcriptional activity of ETS2 ( xref )."

sparser
"USP39 interacts with ETS2 through their respective amino-terminal regions, and the zinc finger and PNT domains are not required for this binding."

sparser
"ETS2 Interacts with USP39 through the Respective Amino-Terminal Regions."

sparser
"To identify the domains responsible for the interaction between ETS2 and USP39, we created several deletion mutants of ETS2:ΔETS (ETS domain-deleted, aa 1–362), PNT-only (Pointed domain-containing, aa 1–170), ΔPNT (Pointed domain-deleted, aa 1–84 & 171–469) and 171–362 (containing aa 171–362) ( xref A)."

reach
"Based on the mutual binding affinity between USP39 and the substrate protein ETS2, as well as its influence on the transcriptional activity of ETS2, we selected USP39 as the candidate DUB for ETS2 and proceeded with further characterization."

sparser
"The results demonstrated that USP39 could bind to ETS2 and all its mutants except 171–362."

sparser
"These findings confirm that USP39 binds to the unspecified amino-terminal region of ETS2, and they indicate that the PNT domain is not required for their interaction."

reach
"To identify the domains responsible for the interaction between ETS2 and USP39, we created several deletion mutants of ETS2:ΔETS (ETS domain-deleted, aa 1–362), PNT-only (Pointed domain-containing, aa 1–170), ΔPNT (Pointed domain-deleted, aa 1–84 & 171–469) and 171–362 (containing aa 171–362) (Figure 3A)."

sparser
"We then examined the interaction between ETS2 and USP39 and USP39 mutants."
CHEK2 affects USP39
4 | 11
4 | 11

sparser
"Additionally, endogenous immunoprecipitation further confirmed that USP39 binds to CHK2 ( Fig. 2 C and D)."

sparser
"Hence, we next examined whether the interaction of USP39 and CHK2 was mediated by DNA damage."

sparser
"In addition, the binding of USP39 and CHK2 didn't change upon Lambda protein phosphatase (λPP) treatment ( Fig. 2 G), suggesting that the interaction between USP39 and CHK2 is independence of DNA dama[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Taken together, our findings suggest that USP39 interacts with CHK2."

sparser
"Since USP39-CHK2 axis regulates cell cycle checkpoint and apoptosis, we next examined the expression of Ki67 and cleaved caspase 3 in these cancer samples."

sparser
"Furthermore, our data shown USP39-CHK2 axis playing an important role in regulation of apoptosis and cell cycle checkpoint induced by DNA damage."

sparser
"Hence, we next examined whether USP39-CHK2 axis affects lung cancer cells response to chemotherapy and radiation."

No evidence text available

sparser
"Thus, we also examined the roles of USP39-CHK2 axis in chemo-radiation response."

sparser
"Hence, our findings suggest that USP39-CHK2 axis may function as the potential biomarker for predicting chemo-radiation response in lung cancer."
FOXM1 affects USP39
3 | 3 8
3 | 3 8

No evidence text available

sparser
"Additionally, the deubiquitinating enzyme USP39 can also directly bind to FOXM1 and further deubiquitinate and stabilize FOXM1."

sparser
"In our work, USP39 interacted with FOXM1 and promoted the splicing of FOXM1 pre-mRNA."

No evidence text available

No evidence text available

reach
"Additionally, the deubiquitinating enzyme USP39 can also directly bind to FOXM1 and further deubiquitinate and stabilize FOXM1."

reach
"We also used RIP assay to confirm that FOXM1 bound with USP39 in human CSCC tissue (Additional file 1: Fig S2B)."

sparser
"The interaction between USP39 and FOXM1 was investigated using co-immunoprecipitation (co-IP) and in vitro deubiquitination analysis."

sparser
"It is worth noting that, as in HCC, USP39 interacts with FOXM1 in BC regulating ubiquitination and stabilizing FOXM1 through competitive bonding with the E3 ubiquitin ligase APC/Cdh1, which regulates BC cell proliferation ( xref )."

sparser
"In general, our research revealed the USP39-FOXM1 axis as a critical driver of breast cancer cell proliferation and provided a theoretical foundation for targeting the USP39-FOXM1 axis for pancreatic cancer treatment."
USP39 affects NPPA
| 13
| 13

sparser
"This dissolution profiles were compared against the USP acceptance criteria for metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"Tablet dissolution was performed using USP dissolution apparatus II as described in the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"The concentrations of metoprolol in the dissolution media were determined per the chromatographic method stated in USP monographs with minor modifications ( USP39-NF34, 2015 )."

sparser
"The drug release studies were performed using USP dissolution apparatus II as established by the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"An extragranular fraction of HPMC K100M was added to achieve the dissolution characteristics that met the USP acceptance criteria for the metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"The chromatographic method was used to determine metoprolol concentration following the USP monographs with minor modifications ( USP39-NF34, 2015 )."

sparser
"This dissolution characteristics was compared against the USP acceptance criteria for metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"These dissolution profiles met the acceptance criteria enumerated in the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"These dissolution characteristics met the acceptance criteria listed in the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"The quantitation of Oxytocin was performed according to the USP monograph of Oxytocin injections with some minor modification ( USP39-NF34, 2015 )."
TRIM26 affects USP39
3 | 7 3
TRIM26 binds USP39.
3 | 5 3
3 | 5 3

sparser
"Intriguingly, USP39 can bind to TRIM26, suggesting that TRIM26 and USP39 governed the balance of ZEB1 expression levels and determined the fate of HCC cells on proliferation and metastasis [153] ."

reach
"More importantly, RNA immunoprecipitation showed that USP39 is bound to TRIM26 mRNA."

No evidence text available

No evidence text available

reach
"Intriguingly, USP39 can bind to TRIM26, suggesting that TRIM26 and USP39 governed the balance of ZEB1 expression levels and determined the fate of HCC cells on proliferation and metastasis [153] ."

No evidence text available

sparser
"USP39 and TRIM26 bind to each other directly and maintain the ubiquitin level of ZEB1, thus determining the proliferation and migration of HCC ( xref )."

sparser
"Additionally, USP39 directly interacts with the E3 ligase TRIM26, which is underexpressed in human HCC tissues, and can inhibit the proliferation and migration of HCC cells."

reach
"In addition, a direct interaction between USP39 and TRIM26 was identified by co-immunoprecipitation and immunofluorescence staining assays, respectively."

reach
"Co-immunoprecipitation assays showed a direct interaction between endogenous USP39 and TRIM26 in SK-hep-1 cells (Fig. 4A)."
TRIM26 inhibits USP39.
| 1
TRIM26 inhibits USP39. 1 / 1
| 1

reach
"Moreover, ubiquitination level of TRIM26 was unaffected by knockdown of USP39 (Supplementary Fig. 4C)."
TRIM26 activates USP39.
| 1
TRIM26 activates USP39. 1 / 1
| 1

reach
"Furthermore, TRIM26 silencing could significantly reverse the reduction of USP39 knockdown cell proliferation, in tumor size and weight (Fig. 8B, C)."
NPPA affects USP39
| 13
| 13

sparser
"This dissolution profiles were compared against the USP acceptance criteria for metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"Tablet dissolution was performed using USP dissolution apparatus II as described in the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"The concentrations of metoprolol in the dissolution media were determined per the chromatographic method stated in USP monographs with minor modifications ( USP39-NF34, 2015 )."

sparser
"The drug release studies were performed using USP dissolution apparatus II as established by the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"An extragranular fraction of HPMC K100M was added to achieve the dissolution characteristics that met the USP acceptance criteria for the metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"The chromatographic method was used to determine metoprolol concentration following the USP monographs with minor modifications ( USP39-NF34, 2015 )."

sparser
"This dissolution characteristics was compared against the USP acceptance criteria for metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"These dissolution profiles met the acceptance criteria enumerated in the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"These dissolution characteristics met the acceptance criteria listed in the USP monograph of metoprolol succinate ER tablets ( USP39-NF34, 2015 )."

sparser
"The quantitation of Oxytocin was performed according to the USP monograph of Oxytocin injections with some minor modification ( USP39-NF34, 2015 )."
USP39 affects syd-2
| 12
USP39 phosphorylates syd-2.
| 8
USP39 phosphorylates syd-2. 8 / 8
| 8

reach
"Using phosphoproteomics, we find SAD-1 phosphorylates SYD-2 on 3 sites that are critical to activate phase separation."

reach
"We conclude that SAD-1 phosphorylates SYD-2 at developing synapses, activating its phase separation and active zone assembly."

reach
"Fortuitously, a SYD-2 phosphopeptide was a top hit present in all 3 biological replicates (Fig 3A), indicating SAD-1 may be responsible for SYD-2 phosphoregulation.To test if SAD-1 was directly responsible for phosphorylating SYD-2 and determine if additional sites may be present that were not found in the phosphoproteomics screen, we performed in vitro kinase assays between SAD-1 and SYD-2 (Figs 3B, S4A, and S4B and S2 Table)."

reach
"Our data suggest SYD-2 phosphorylation by SAD-1 activates the protein to phase separate and assemble the presynaptic active zone."

reach
"We determine SAD-1 phosphorylation of SYD-2 at three sites is critical to activate its phase separation."

reach
"We conclude that SAD-1 phosphorylates SYD-2 at developing synapses, enabling its phase separation and active zone assembly."

reach
"Fortuitously, a SYD-2 phosphopeptide was a top hit present in all 3 biological replicates (Figure 3A), indicating SAD-1 may be responsible for SYD-2 phosphoregulation.To test if SAD-1 was directly responsible for phosphorylating SYD-2 and determine if additional sites may be present not found in the phosphoproteomics screen, we performed in vitro kinase assays between SAD-1 and SYD-2 (Figure 3B and S3A-B)."

reach
"Our data suggest SYD-2 phosphorylation by SAD-1 activates the protein to phase separate and assemble the presynaptic active zone."
USP39 increases the amount of syd-2.
| 2
USP39 increases the amount of syd-2. 2 / 2
| 2

reach
"In the 3A phosphomutant, SAD-1 was not able to increase levels of SYD-2, UNC-10, and synaptic vesicles at HSN presynapses (Fig 5A and 5B), as seen in a wild-type background."

reach
"In the 3A phosphomutant, SAD-1 was not able to increase levels of SYD-2, UNC-10, and synaptic vesicles at HSN presynapses (Figure 5A-B) as seen in a wildtype background."
USP39 activates syd-2.
| 2
USP39-T202E activates syd-2. 2 / 2
| 2

reach
"In addition, we find that overexpression of constitutively active SAD-1(T202E) increases the accumulation of SYD-2, downstream active zone components, and synaptic vesicle marker RAB-3 at synapses (Figs 2A and 2B and S3)."

reach
"In addition, we find that overexpression of constitutively active SAD-1(T202E) increases the accumulation of SYD-2, downstream active zone components, and synaptic vesicle marker RAB-3 at synapses (Figure 2A-B and Figure S2)."
| 1 10
| 1 10

reach
"The deacetylation of USP39 by SIRT7 promotes the stability and thereby accelerates cell proliferation and tumorigenesis of HCC [10] ."

reach
"To further examine how USP39 promotes tumorigenesis in vivo, tumor and para-tumor tissues collected from Usp39 and WT mice were analyzed by transcriptome sequencing."

eidos
"USP39 promotes tumorigenesis by stabilizing and deubiquitinating SP1 protein in hepatocellular carcinoma ."

reach
"USP39 promotes tumorigenesis partially through a splicing switch of KANK2."

reach
"An increasing amount of evidence has demonstrated that the aberrant expression of USP39 promotes tumorigenesis and is associated with HCC progression [13, 14]."

reach
"The de-acetylation of USP39 by SIRT7 can promote its stability and thereby accelerate HCC cell proliferation and tumorigenesis."

reach
"Growing evidence indicates that abnormal expression of USP39 contributes to tumorigenesis and is linked to HCC progression ."

reach
"et al. have reported that overexpression of USP39 predicts poor prognosis and promotes tumorigenesis of prostate cancer [7] ."

reach
"In HCC, SIRT7-mediated deacetylation impedes MYST1-facilitated acetylation of USP39, which is a prerequisite for its E3 ligase-induced degradation [55] and accelerates the tumorigenesis of HCC."

reach
"To elucidate the underlying mechanism of USP39-mediated tumorigenesis of PC, we examined the activation of multiple signaling pathways."
SP1 affects USP39
3 | 8
3 | 8

sparser
"Then, we used nude mice to establish a cancer xenograft model to demonstrate that the function of USP39-SP1 axis in tumor growth."

sparser
"Miyamoto-Sato's study found that USP39 and SP1 protein may interact with each other in a dataset of protein-protein interactions (PPIs) network [14] ."

sparser
"This provides an effective anti-tumor therapeutic strategy of HCC by an understanding of the USP39-SP1 protein axis."

sparser
"Next, we extended our analysis by investigating whether endogenous USP39 and SP1 can interact with each other."

sparser
"Together, these results suggest that USP39 directly interacts with SP1 protein."

sparser
"Co-IP assay was used to test the binding of the full-length USP39 and SP1 (wildtype) and the deletion mutants in 293 T cells."

sparser
"SP1 binds to C-terminal domain (amino acids 200–565) of USP39 (Supplementary Material Fig. 1 B)."

No evidence text available

sparser
"Interaction of USP39 and SP1 plays an important role in promoting cell proliferation, cell cycle, and tumor growth of HCC."

No evidence text available
USP39 affects PGK1
1 | 2 7
USP39 binds PGK1.
1 | 7
1 | 7

sparser
"Histone lactylation can also enhance USP39 expression, which interacts with the key glycolytic enzyme phosphoglycerate kinase 1 (PGK1) to promote its stability and deubiquitination, thereby increasing PGK1’s biological activity and potentially accelerating the glycolytic pathway."

sparser
"For example, in bladder cancer, H3K18 lactylation promotes tumorigenesis by enhancing the expression of the oncogene Lipocalin-2 (LCN2) ( xref ); in endometrial cancer, histone lactylation upregulates USP39 expression, which further interacts with PGK1 to activate the PI3K/AKT/HIF-1α signaling pathway, accelerating tumor progression ( xref ); in colorectal cancer, the activation of G-protein coupled receptor 37 (GPR37) promotes the expression of LDHA by activating the Hippo pathway, thereby intervening in tumor progression ( xref )."

No evidence text available

sparser
"A reciprocal IP experiment and a reciprocal assay confirmed that PGK1 and USP39 interacted with each other."

sparser
"USP39 interacts with PGK1, thereby activating the PI3K/AKT/HIF-1α signaling pathway, enhancing glycolysis and lactylation, and establishing a carcinogenic positive feedback cycle ( xref ) ( xref )."

sparser
"Researchers have identified the interaction between USP39 and PGK1 using Co-IP and mass spectrometry(MS), and the downregulation of USP39 leads to a decrease in PGK1 protein levels in EC cells."

sparser
"As a deubiquitinase, USP39 specifically interacts with the glycolytic enzyme PGK1 (validated by co-immunoprecipitation coupled with mass spectrometry), stabilizing PGK1 protein levels via deubiquitination [ xref ]."

sparser
"Phosphoglycerate kinase 1 (PGK1), the first ATP-generating enzyme in the glycolytic pathway, has been reported to activate the PI3K/AKT pathway and was chosen for further binding validation by investigating whether endogenous USP39 and PGK1 could interact with each other."
USP39 deubiquitinates PGK1.
| 2
USP39 leads to the deubiquitination of PGK1. 2 / 2
| 2

reach
"Conversely, the USP39 knockdown increased PGK1 ubiquitination in EC cells (Fig. 8H), indicating that USP39 is responsible for PGK1 deubiquitination."

reach
"Ectopic expression of Flag-USP39 markedly promoted PGK1 de-ubiquitination (Fig. 8G)."
USP39 affects NAT10
| 1 9
| 1 9

sparser
"Moreover, the GST pulldown assay showed that G‐749 treatment reduces the in vitro binding of USP39 to NAT10 protein (Figure  xref ; Figure xref , Supporting Information)."

sparser
"The interaction between NAT10 and USP39 was further confirmed by Co-IP (Fig. xref and Fig. xref )."

sparser
"First, the specific mechanism underlying the LPS-mediated enhancement of USP39 and NAT10 interactions remains unclear."

reach
"This Khib modification, in turn, promoted the interaction between NAT10 and the deubiquitinase USP39, thereby enhancing NAT10 protein stability and upregulating NAT10."

sparser
"Our previous studies have shown that the deubiquitin ligase Ubiquitin‐specific Peptidase 39 (USP39) directly interacts with NAT10 in a molecule‐specific manner to enhance the stability of NAT10. [ xref ] The results from co‐immunoprecipitation demonstrated a strong interaction between exogenous expression of NAT10 and USP39, whereas the interaction was weakened by G‐749 (Figure  xref )."

sparser
"This Khib modification, in turn, promoted the interaction between NAT10 and the deubiquitinase USP39, thereby enhancing NAT10 protein stability and upregulating NAT10."

sparser
"This modification enhances the interaction between NAT10 and USP39, leading to improved stability of the NAT10 protein [ xref ]."

sparser
"As a medium for NAT10 to interact with the deubiquitinase USP39, LINC00623 can bind to NAT10 and recruit USP39, thereby improving NAT10 stability by blocking its ubiquitination and degradation."

sparser
"Further pharmacological research indicated that G‐749 significantly weakened the interaction between NAT10 and the deubiquitinating ligase USP39, leading to the degradation of NAT10 in a proteasome‐dependent manner."

sparser
"LPS stabilizes NAT10 by promoting NAT10-USP39 interaction and reducing proteasomal degradation."
Bqt1 affects USP39
| 9
| 9

reach
"Thus, Bqt1 alone associates with Sad1 but is not sufficient to connect Sad1 to Rap1."

reach
"When Sad1 was overexpressed in these cells, the protein was observed along to the nuclear envelope rather than just at the SPB, and Bqt1 was also observed at the nuclear envelope ( Figure 4 E), which [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Similarly, Bqt1 binds to the SPB component Sad1 [19] ."

reach
"In the absence of Bqt1, Bqt2-GFP showed diffuse staining throughout the nucleus and was not localized at the telomere nor at the SPB ( Figure 3 D), indicating that Bqt2 localization at either the telo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Taken together, these results showed that Bqt1 directly binds to Bqt2 and to Sad1 and that Bqt2 binds to Sad1 through interaction with Bqt1."

reach
"Our results demonstrate that Bqt1 and Bqt2 together form a bridge between Sad1 and Rap1: Bqt1 binds to Sad1, Bqt2 bind to Bqt1, and a complex of Bqt1 and Bqt2 binds to Rap1."

reach
"Two-hybrid and coimmunoprecipitation experiments showed that Bqt1 directly binds the SPB component Sad1."

reach
"Bqt2 lacks this ability but binds Sad1 bound Bqt1."

reach
"These results provide an initial scheme for connecting telomeres with the SPB: Sad1 binds Bqt1, which recruits Bqt2, forming the complex that binds Rap1, thus gluing the Rap1 bound telomere to Sad1 ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
| 7

reach
"Zhao et al. further indicated that USP39 promoted the proliferation of ESCC cells by enhancing the splicing and maturation of Rictor mRNA, a component of the mTOR complex, and regulating the mTORC2 signaling pathway [50]."

reach
"Moreover, USP39 activated PI3K/AKT/HIF-1alpha signaling pathway via interacting with and stabilizing PGK1 to stimulate glycolysis."

reach
"Mechanistically, histone lactylation promoted the expression of ubiquitin-specific peptidase 39 (USP39), which interacted with, stabilized, and de-ubiquitinated phosphoglycerate kinase 1 (PGK1), thereby activating the PI3K/AKT/HIF-1α signaling pathway."

reach
"In turn, histone lactylation regulated the expression of USP39, and USP39 activated the PI3K/AKT/HIF-1α signaling pathway by interacting with PGK1."

reach
"Here, we prove that USP39 promotes HCC cell proliferation and migration by directly deubiquitin beta-catenin, a key molecular of Wnt/beta-catenin signaling pathway whose abnormal expression or activation results in several tumors, following its co-localization with USP39."

reach
"Histone lactylation and USP39 accelerate glycolysis by activating the PI3K/AKT/HIF-1alpha signaling pathway in EC."

reach
"Previous studies have reported that USP39 silencing inhibits colon cancer cell growth and metastasis, and induces apoptosis by regulating the Wnt/β-catenin signaling pathway [31]."
| 2

reach
"USP39 down-regulates the p53/p21 signaling pathway and stabilizes CDK1 and cyclin B1 to promote the proliferation of ovarian cancer cells [34]."

reach
"USP39 knockdown induces cell apoptosis via the regulation the Wnt/β-catenin signaling pathway in colorectal cancer [31]."
USP39 affects bqt1
| 9
| 9

reach
"Thus, Bqt1 alone associates with Sad1 but is not sufficient to connect Sad1 to Rap1."

reach
"When Sad1 was overexpressed in these cells, the protein was observed along to the nuclear envelope rather than just at the SPB, and Bqt1 was also observed at the nuclear envelope ( Figure 4 E), which [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Similarly, Bqt1 binds to the SPB component Sad1 [19] ."

reach
"In the absence of Bqt1, Bqt2-GFP showed diffuse staining throughout the nucleus and was not localized at the telomere nor at the SPB ( Figure 3 D), indicating that Bqt2 localization at either the telo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Taken together, these results showed that Bqt1 directly binds to Bqt2 and to Sad1 and that Bqt2 binds to Sad1 through interaction with Bqt1."

reach
"Our results demonstrate that Bqt1 and Bqt2 together form a bridge between Sad1 and Rap1: Bqt1 binds to Sad1, Bqt2 bind to Bqt1, and a complex of Bqt1 and Bqt2 binds to Rap1."

reach
"Two-hybrid and coimmunoprecipitation experiments showed that Bqt1 directly binds the SPB component Sad1."

reach
"Bqt2 lacks this ability but binds Sad1 bound Bqt1."

reach
"These results provide an initial scheme for connecting telomeres with the SPB: Sad1 binds Bqt1, which recruits Bqt2, forming the complex that binds Rap1, thus gluing the Rap1 bound telomere to Sad1 ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects STAT1
1 | 6 2
USP39 increases the amount of STAT1.
| 5
USP39 increases the amount of STAT1. 5 / 5
| 5

reach
"Knockdown of USP39 Inhibits STAT1 Expression."

reach
"These results indicate that USP39 knockdown may inhibit STAT1 expression."

reach
"This is the first study, to our knowledge, to provide evidence that USP39 may promote the development of HNSCC by regulating STAT1 expression."

reach
"The results showed that compared with the control group, USP39 knockdown significantly reduced STAT1 mRNA levels (Figure 6)."

reach
"Conclusion: Our findings indicated that USP39 knockdown may inhibit HNSCC viability and migration by suppressing STAT1 expression."
USP39 binds STAT1.
1 | 1 2
1 | 1 2

sparser
"Furthermore, USP39 interacts with STAT1 and removes K6-linked ubiquitin chains, thereby stabilizing the STAT1 protein ( xref )."

reach
"A recent report describes how USP39 is able to bind nuclear-localized STAT1 and sustain the STAT1 protein level by deubiquitination; consequently, this is a means to export deubiquitinated STAT1 from the nucleus to the cytoplasm by avoiding its degradation ."

sparser
"In the host antiviral defense mechanism, USP39 interacts with STAT1, resulting in a notable reduction in the ubiquitination of the K6-linkage, but not the K48-linkage, of STAT1."

No evidence text available
USP39 affects Histone
| 7 2
| 7 2

reach
"These results indicate that the interaction between Sad1 and histones is required for the distribution of Sad1 in the nuclear envelope but not for its localization to the SPB."

reach
"We next investigated whether the interaction between Sad1 and histones is important for the centromere-NE association."

reach
"These data indicate that the interaction between Sad1 and histone is not involved in centromere clustering at SPB, which is consistent with the previous finding that Sad1 is essential for linking centromeres with SPB ."

sparser
"To further examine whether histone could bind to the USP39 promoter active region in vitro, an EMSA was conducted."

reach
"These results indicated that histone indeed bound to the predicted promoter active region binding site of USP39 in vitro."

reach
"We hypothesize that these nuclear membrane proteins may form a synergistic network to create a microenvironment to benefit heterochromatin organization and maintenance at the nuclear periphery, which requires further investigation.Fission yeast Sad1 binds both canonical histone H2A-H2B and histone variant H2A.Z-H2B, whereas the budding yeast SUN-family protein, Mps3, specifically recognizes H2A.Z ."

sparser
"These results indicated that histone indeed bound to the predicted promoter active region binding site of USP39 in vitro."

reach
"To examine the effect of 5 R mutation on the interaction between Sad1 and histone in vivo, we created a stain carrying Sad1-5R-HA and H2B -FLAG and conducted Co-IP experiments."

reach
"8b, c), indicating that Sad1 associates with heterochromatin regions.Next, we wanted to test whether the histone binding activity of Sad1 is important for heterochromatin silencing."
USP39 affects E
4 | 5
USP39 binds E. 9 / 9
4 | 5

No evidence text available

sparser
"Taken together, these results suggested that USP39 directly and specifically interacts with the E protein through the AR motif and performs its deubiquitination function using the iUSP motif."

No evidence text available

No evidence text available

No evidence text available

sparser
"However, it was also found that USP39 interacts with the E protein, a highly conserved envelope protein of SARS-CoV-2, through its N-terminal arginine-rich modality, which reduces polyubiquitination of the E protein and protects it from degradation."

sparser
"Moreover, the interaction of USP39 and the E protein was readily detectable in reciprocal co-immunoprecipitation (co-IP) experiments ( Fig. 3 B and C)."

sparser
"A fluorescence resonance energy transfer (FRET) assay also showed the direct interaction of USP39 and the E protein, that is, bleaching of the fluorescence from E-yellow fluorescent protein (YFP) enha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Similar to the above results, we also demonstrated that USP39 directly interacts with the substrate E protein via the AR motif, while the iUSP domain not required for E binding is required for E deubi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects AKT
| 6 3
USP39 phosphorylates AKT.
| 2 3
USP39 leads to the phosphorylation of AKT. 5 / 5
| 2 3

sparser
"USP39 effectively induced phosphorylation of PI3 K and AKT and increased the expression of HIF-1α in EC cells."

sparser
"Mechanistic analyses indicate that USP39 promotes the phosphorylation of AKT, EGFR, and cyclin B1, while it deters the activation of PARP and Caspase-3, thereby enhancing cell proliferation, migration, and invasion, and curbing apoptosis [ xref ]."

reach
"Mechanistic analyses indicate that USP39 promotes the phosphorylation of AKT, EGFR, and cyclin B1, while it deters the activation of PARP and Caspase-3, thereby enhancing cell proliferation, migration, and invasion, and curbing apoptosis [78]."

sparser
"USP39 efficiently induced the phosphorylation of PI3K and AKT and increased HIF-1α expression in EC cells (Fig. xref )."

reach
"USP39 efficiently induced the phosphorylation of PI3K and AKT and increased HIF-1α expression in EC cells (Fig. 7A, B)."
USP39 inhibits AKT.
| 2
USP39 inhibits AKT. 2 / 2
| 2

reach
"Mechanistically, downregulation of USP39 blocked the activation of Akt and extracellular signal regulated kinase signaling pathways in RCC cells."

reach
"Moreover, depletion of USP39 blocked activation of Akt, mTOR, p53, and PARP signaling pathways."
USP39 activates AKT.
| 2
USP39 activates AKT. 2 / 2
| 2

reach
"In addition, USP39 silencing blocked the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B pathway (AKT) by regulating SIRT2."

reach
"Collectively, these results indicate that histone lactylation and USP39 promote PI3K/AKT- and HIF-1α-mediated glycolysis in EC cells."
E affects USP39
4 | 5
USP39 binds E. 9 / 9
4 | 5

No evidence text available

sparser
"Taken together, these results suggested that USP39 directly and specifically interacts with the E protein through the AR motif and performs its deubiquitination function using the iUSP motif."

No evidence text available

No evidence text available

No evidence text available

sparser
"However, it was also found that USP39 interacts with the E protein, a highly conserved envelope protein of SARS-CoV-2, through its N-terminal arginine-rich modality, which reduces polyubiquitination of the E protein and protects it from degradation."

sparser
"Moreover, the interaction of USP39 and the E protein was readily detectable in reciprocal co-immunoprecipitation (co-IP) experiments ( Fig. 3 B and C)."

sparser
"A fluorescence resonance energy transfer (FRET) assay also showed the direct interaction of USP39 and the E protein, that is, bleaching of the fluorescence from E-yellow fluorescent protein (YFP) enha[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Similar to the above results, we also demonstrated that USP39 directly interacts with the substrate E protein via the AR motif, while the iUSP domain not required for E binding is required for E deubi[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
Bisphenol A affects USP39
8 |
Bisphenol A increases the amount of USP39.
4 |
Bisphenol A increases the amount of USP39. 4 / 4
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
Bisphenol A decreases the amount of USP39.
4 |
Bisphenol A decreases the amount of USP39. 4 / 4
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP39 affects SRPK1
4 | 3 1
USP39 binds SRPK1.
4 | 1 1
4 | 1 1

No evidence text available

No evidence text available

sparser
"USP39 binds SRPK1 (Serine/arginine-rich splicing factor kinase 1) through its 101–565 fragment, promoting SRPK1-SRSF1 (Serine and arginine-rich splicing factor 1) phosphorylation and interaction, which subsequently regulates VEGF-A165b alternative splicing to drive RCC proliferation and angiogenesis ( xref )."

No evidence text available

reach
"The interaction between USP39 and SRPK1/SRSF1 was analyzed by Western blot using anti-Flag tag (Abcam) or anti-SRSF1 (Abcam)."

No evidence text available
USP39 inhibits SRPK1.
| 1
USP39 inhibits SRPK1. 1 / 1
| 1

reach
"In particular, USP39 de-ubiquitinates and stabilizes CHK2 to regulate the DNA damage response and chemical radiation resistance [43], de-ubiquitinates and stabilizes the SP1 protein to promote hepatocellular carcinoma progression [44], and inhibits VEGF-A165b-selective splicing by regulating SRSF1 and SRPK1 to promote malignant proliferation and angiogenesis of renal cell carcinoma [45]."
USP39 activates SRPK1.
| 1
USP39 activates SRPK1. 1 / 1
| 1

reach
"In renal cancer cells (RCCs), USP39 promotes malignant progression by regulating the anti-angiogenic variant of vascular endothelial growth factor A (VEGF-A), VEGF-A b, in addition to the RNA splicing-related proteins SRSF1 and SRPK1 [90]."
USP39 affects RBM39
3 | 1 4
USP39 binds RBM39.
3 | 4
3 | 4

sparser
"Biochemical experiments verify that USP39 and RBM39 interact with each other and highly colocalize in the nucleus."

sparser
"Our proteomics and DUB screening experiments demonstrated that USP39 interacted with RBM39 and upregulated its protein level."

No evidence text available

sparser
"After we demonstrated the interaction between USP39 and RBM39, we sought to test whether and how USP39 regulates RBM39 in gastric cancer cells."

No evidence text available

sparser
"Lu et al. found that USP39 can interact with RBM39 and stabilize it through removal of the polyubiquitin chain by K48 deubiquitination, therefore promoting tumor progression ( xref )."

No evidence text available
USP39 inhibits RBM39.
| 1
USP39 inhibits RBM39. 1 / 1
| 1

reach
"Deubiquitinating enzyme USP39 promotes the growth and metastasis of gastric cancer cells by modulating the degradation of RNA-binding protein RBM39."
| 5

reach
"Here, our in vitro and in vivo experimental data showed that overexpression of USP39 significantly enhanced PC cells proliferation, whereas knockdown of USP39 suppressed PC cells proliferation."

reach
"Cai et al. [52] reported that USP39 promotes PC cell apoptosis by regulating the AKT signaling pathway."

reach
"Although our results suggested that high USP39 expression was closely associated with PC, but the precise mechanism by which USP39 promotes the tumorgenesis of PC remains to be further explored."

reach
"As shown in Fig. 2 B–C, we found that USP39-overexpressing cells showed a significantly higher in vitro proliferation rate than vector-transfected cells and knockdown of USP39 obviously suppressed the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"These data collectively indicate that USP39 promotes the tumorigenicity of PC cells in vitro and in vivo ."
| 3

reach
"Consistent with these findings, our data revealed that silencing of USP39 promotes PC cell apoptosis."

reach
"Consistent with the clinical correlation of USP39 in PC, the ectopic introduction of USP39 significantly enhanced proliferation of PC cells in vitro and in vivo , whereas knockdown of USP39 suppressed[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Together, these results indicate that the death of PC cells caused by the silencing USP39 through inhibition of AKT signaling pathway to a certain extent.MicroRNAs have been functionally classified as[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects GLI1
| 7 1
USP39 increases the amount of GLI1.
| 5 1
USP39 increases the amount of GLI1. 6 / 6
| 5 1

reach
"USP39 undergoes LLPS in the nucleolus and promotes tumor progression by regulating GLI1 expression."

sparser
"To investigate the regulation of GLI1 transcription by USP39, we performed GLI1 promoter luciferase reporter assay to assess the influence of USP39 on the transcription of GLI1."

reach
"USP39 knockdown suppresses GLI1 expression."

reach
"Furthermore, USP39 knockdown suppresses the expression of oncogenic transcription factor GLI1, which can also be reverted by USP39 complementation."

reach
"Moreover, knockdown of USP39 reduced oncogenic transcription effector GLI1 levels."

reach
"Consistently, the results showed that USP39 knockdown reduced GLI1 levels, which were reversed in USP39 rescue groups (Fig. 5G, H)."
USP39 inhibits GLI1.
| 1
USP39 inhibits GLI1. 1 / 1
| 1

reach
"These in vivo results are in accordance with our in vitro data, suggesting that USP39 functions as a tumor-promoting DUB and USP39 knockdown elicits suppressive effects on lung cancer growth by downregulating GLI1."
USP39 activates GLI1.
| 1
USP39 activates GLI1. 1 / 1
| 1

reach
"The restoration of USP39 expression increased the staining intensity of both GLI1 and Ki67 as compared to samples from USP39 knockdown group (Fig. 7D)."
USP39 affects Circulin-C
| 8

sparser
"The head-to-tail splicing of circ-USP39 was verified by agarose gel electrophoresis."

sparser
"This study aims to explore the effect of circ-USP39 on hypoxia-induced cardiomyocyte injury."

sparser
"The interactions between miR-499b-5p and circ-USP39 (or acyl-CoA synthetase long-chain family member-1 (ACSL1) ) were verified by luciferase reporter assays."

sparser
"However, the role of circRNA hsa_circ_0055440 (circ-USP39) in acute myocardial infarction regulation has not been studied yet."

sparser
"After confirming the circular characteristics of circ-USP39, we further found that the circ-USP39 expression was upregulated in hypoxia-induced cardiomyocytes and the circ-USP39 knockdown facilitated the viability of hypoxia-induced AC16, while suppressing cardiomyocyte apoptosis and injury."

sparser
"Importantly, circ-USP39 negatively regulated miR-499b-5p expression."

sparser
"As a downstream target of miR-499b-5p, ACSL1 partially counteracted the protective effect of circ-USP39 depletion on cardiomyocyte injury."

sparser
"Silencing of circ-USP39 alleviates hypoxia-induced cardiomyocyte injury via the miR-499b-5p/ACSL1 axis."
PGK1 affects USP39
1 | 7
1 | 7

sparser
"Histone lactylation can also enhance USP39 expression, which interacts with the key glycolytic enzyme phosphoglycerate kinase 1 (PGK1) to promote its stability and deubiquitination, thereby increasing PGK1’s biological activity and potentially accelerating the glycolytic pathway."

sparser
"For example, in bladder cancer, H3K18 lactylation promotes tumorigenesis by enhancing the expression of the oncogene Lipocalin-2 (LCN2) ( xref ); in endometrial cancer, histone lactylation upregulates USP39 expression, which further interacts with PGK1 to activate the PI3K/AKT/HIF-1α signaling pathway, accelerating tumor progression ( xref ); in colorectal cancer, the activation of G-protein coupled receptor 37 (GPR37) promotes the expression of LDHA by activating the Hippo pathway, thereby intervening in tumor progression ( xref )."

No evidence text available

sparser
"A reciprocal IP experiment and a reciprocal assay confirmed that PGK1 and USP39 interacted with each other."

sparser
"USP39 interacts with PGK1, thereby activating the PI3K/AKT/HIF-1α signaling pathway, enhancing glycolysis and lactylation, and establishing a carcinogenic positive feedback cycle ( xref ) ( xref )."

sparser
"Researchers have identified the interaction between USP39 and PGK1 using Co-IP and mass spectrometry(MS), and the downregulation of USP39 leads to a decrease in PGK1 protein levels in EC cells."

sparser
"As a deubiquitinase, USP39 specifically interacts with the glycolytic enzyme PGK1 (validated by co-immunoprecipitation coupled with mass spectrometry), stabilizing PGK1 protein levels via deubiquitination [ xref ]."

sparser
"Phosphoglycerate kinase 1 (PGK1), the first ATP-generating enzyme in the glycolytic pathway, has been reported to activate the PI3K/AKT pathway and was chosen for further binding validation by investigating whether endogenous USP39 and PGK1 could interact with each other."
H2AC20 affects USP39
| 8
H2AC20 activates USP39.
| 5
H2AC20 activates USP39. 4 / 4
| 4

reach
"H2A-H2B promotes Sad1 phase separation."

reach
"Together, these data demonstrate that H2A-H2B promotes Sad1 phase separation to enrich Sad1-interaction partners, such as HDACs, in the same condensates.Collectively, we propose the following model for Sad1’s role in heterochromatin positioning and formation: H2A-H2B interacts with Sad1 and facilitates the otherwise-dispersed Sad1 clustering into condensates, forming discrete Sad1 puncta distributed on the NE as observed in Fig. 3; liquid droplet-like condensates formed by Sad1-H2A-H2B help recruit heterochromatin factors, such as Clr3 and Sir2, to the condensates, which promotes spatial organization and heterochromatin silencing at the nuclear envelope (Fig. 7c)."

reach
"H2A-H2B enhances the phase separation ability of Sad1, which in turn facilitates the recruitment of heterochromatin factors."

reach
"We hypothesized that H2A-H2B might promote Sad1 phase separation to recruit heterochromatin factors to the same condensates to facilitate heterochromatin organization."
H2AC20 bound to USP39 activates USP39. 1 / 1
| 1

reach
"Our results revealed a nucleosome-independent function of H2A-H2B: H2A-H2B physically associates with Sad1 to regulate Sad1’s interaction with other factors, such as Sir2 and Clr3, and promote the LLPS ability of Sad1."
H2AC20 binds USP39.
| 3
| 3

reach
"The interaction between Sad1 and H2A-H2B was also held when the GST pull-down assay was performed using a single-chain fusion of H2A and H2B (hereafter referred to as H2AB) (Supplementary Fig. 1b), which has been shown to be structurally similar to the wild type H2A-H2B heterodimer ."

reach
"Our results revealed a nucleosome-independent function of H2A-H2B: H2A-H2B physically associates with Sad1 to regulate Sad1’s interaction with other factors, such as Sir2 and Clr3, and promote the LLPS ability of Sad1."

reach
"We solved the crystal structure of the histone binding motif (HBM) of Sad1 in a complex with a H2A-H2B fusion protein and showed that the DEF/Y motif of Sad1 binds H2A-H2B."
H2AB affects USP39
| 8
H2AB binds USP39.
| 6
USP39 binds H2AB. 6 / 6
| 6

reach
"Isothermal titration calorimetry (ITC) assays further confirmed that Sad1 bound H2AB and H2AZB with comparable dissociation constants (K ) of 9.5 μM and 7.5 μM, respectively (Fig. 1c), indicating that Sad1 does not have a binding preference for H2A or H2A.Z."

reach
"To reveal the structural basis of the interaction between Sad1 and H2AB, we first dissected the structural elements of Sad1 required for the Sad1-H2AB interaction."

reach
"The binding between Sad1 and H2AB is mediated by electrostatic and hydrophobic interactions (Figs."

reach
"The Sad1 F118A mutation destabilized the Sad1-H2AB complex, and the substitution of Sad1 F118 with a positively charged arginine residue (F118R) severely diminished the interaction between Sad1 and H2AB (Fig. 2d)."

reach
"In addition, charge-reverse mutations of D114 and E117 decreased binding affinity between Sad1 and H2AB by 5.6-fold (Fig. 2d)."

reach
"By screening some known silencing factors, our in vitro pull-down assays identified that Clr3 and Sir2 directly interact with the Sad1-H2AB complex (Figs."
H2AB activates USP39.
| 2
H2AB activates USP39. 2 / 2
| 2

reach
"Fluorescence images of mixed H2AB-RFP and Sad1 -GFP proteins showed that H2AB substantially augmented the phase separation of Sad1 -GFP (Fig. 6k–m)."

reach
"Moreover, it is worth noting that the 147-bp nucleosome core particle (NCP) was not able to promote the phase separation of Sad1 (Supplementary Fig. 12b), suggesting that H2AB-dependent augmentation of Sad1 phase separation relies on its specific interaction with the free H2A-H2B."
Circulin-C affects USP39
| 8

sparser
"The head-to-tail splicing of circ-USP39 was verified by agarose gel electrophoresis."

sparser
"This study aims to explore the effect of circ-USP39 on hypoxia-induced cardiomyocyte injury."

sparser
"The interactions between miR-499b-5p and circ-USP39 (or acyl-CoA synthetase long-chain family member-1 (ACSL1) ) were verified by luciferase reporter assays."

sparser
"However, the role of circRNA hsa_circ_0055440 (circ-USP39) in acute myocardial infarction regulation has not been studied yet."

sparser
"After confirming the circular characteristics of circ-USP39, we further found that the circ-USP39 expression was upregulated in hypoxia-induced cardiomyocytes and the circ-USP39 knockdown facilitated the viability of hypoxia-induced AC16, while suppressing cardiomyocyte apoptosis and injury."

sparser
"Importantly, circ-USP39 negatively regulated miR-499b-5p expression."

sparser
"As a downstream target of miR-499b-5p, ACSL1 partially counteracted the protective effect of circ-USP39 depletion on cardiomyocyte injury."

sparser
"Silencing of circ-USP39 alleviates hypoxia-induced cardiomyocyte injury via the miR-499b-5p/ACSL1 axis."
USP39 affects Glioma
| 7
USP39 activates Glioma.
| 5
USP39 activates Glioma. 5 / 5
| 5

reach
"Besides, Ding et al. firstly reported that USP39 acted as an oncogene to promote glioma progression and provided a new therapeutic target for glioma [19]."

reach
"USP39 can also promote the development of glioma by inducing the maturation of TAZ mRNA to increase its protein level [14]."

reach
"USP39 promotes glioma cells proliferation via Cyclin B1."

reach
"USP39 promotes the progression of glioma xenografts in nude mice."

reach
"The similar mechanism of USP39 was also found in human glioma in which USP39 could induce ADAM9 mRNA maturation but not protein to promote glioma progression [53]."
USP39 inhibits Glioma.
| 2
USP39 inhibits Glioma. 2 / 2
| 2

reach
"We reported similar results in our previous study, in which knockdown of USP39 suppressed the glioma cell migration and invasion in vitro and inhibited glioma growth and invasion in vivo [12]."

reach
"Besides, the expression of SOX2, a molecular marker of glioma stem cells, was reduced in the U251 cells transfected with USP39 siRNA (data not shown), indicating USP39 might also inhibit the stemness of glioma cells."
USP39 affects GST
| 7
| 7

sparser
"The result showed that the K29-linked ubiquitination of Cyclin B1 was significantly reducible after incubated with GST-USP39 protein, suggesting that USP39 directly deubiquitinates Cyclin B1 ( xref d)."

sparser
"Given that GSTUSP39 also exhibited slight binding affinity for other tested ubiquitins, we do not exclude the possibility that USP39 serves as a reader of Lys‐linked chains in cellulo ."

sparser
"The pulldown assay further revealed that GSTUSP39 interacted most strongly with Dap20‐linked diUb, suggesting that USP39 might serve as its reader at least in vitro."

sparser
"The eluate was sequentially incubated with GST-USP39 protein or GST protein followed by detection of K29 linked-CycB1 using anti-HA antibody with Western blotting."

sparser
"To further investigate whether USP39 directly deubiquitinated CHK2, bacterially purified GST-USP39 and ubiquitinated CHK2 proteins were incubated together in a cell-free system."

sparser
"We found that GSTUSP39 did not cleave Dap20‐linked diUb, whereas the pan‐deubiquitinase USP2cc readily cleaved it, suggesting that USP39 did not deubiquitinate at least Dap20‐linked ubiquitin chains (Figure  xref )."

sparser
"To test whether the Cyclin B1-USP39 interaction was direct, we performed GST-pull down assays using GST-USP39 and Flag-CycB1."
USP39 affects Flag
| 7
| 7

sparser
"The results indicated that Myc-SP1 was successfully co-immunoprecipitated by Flag-USP39 wild type and mutation type, suggesting an interaction between the two exogenously expressed proteins ( Fig. 4 A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The results of Co-IP revealed that Flag-USP39 was significantly enriched in the precipitates of Myc-SIRT7 and vice versa, which indicated that USP39 interacted with SIRT7 in CaSki and SiHa cells (Fig.  xref B)."

sparser
"Flag‐USP33, Flag‐RNF5, Flag‐USP32, and FlagUSP39 were purchased from SinoBiological, and USP33 was then cloned into pCAGGS or pLVX with different tags."

sparser
"We co-expressed Flag-USP39 wild type (WT) and C306A (CA) mutant type (catalytic inactive), and Myc-SP1 constructs in 293 T cells and performed co-IP analysis."

sparser
"HA-ubiquitin and His-PGK1 constructs were co-expressed, with or without Flag-USP39, in Ishikawa and KLE cells."

sparser
"Ectopic expression of Flag-USP39 markedly promoted PGK1 de-ubiquitination (Fig. xref )."

sparser
"To identify whether two proteins are co-localized to the same subcellular compartments, HepG2 cells were immune-stained with Flag-USP39 and Myc-SP1 antibody and visualized by fluorescence microscopy."
TP53 affects USP39
1 | 3 3
TP53 binds USP39.
1 | 2 3
1 | 2 3

sparser
"USP39 indirectly regulates MDM2 or directly binds to p53, affecting its stability and transcriptional activity, and inhibiting tumor suppressive function [ xref ]."

reach
"Given the importance of the p53 pathway in the tumor promotor function of USP39, further investigations should address these key questions : (1) How does USP39 regulate p53 and what is the interaction between USP39 and p53?"

sparser
"Given the importance of the p53 pathway in the tumor promotor function of USP39, further investigations should address these key questions: (1) How does USP39 regulate p53 and what is the interaction between USP39 and p53? (2) is the oncogenic function of USP39 solely dependent on the p53 pathway, or is another signaling pathway involved?"

No evidence text available

reach
"In osteosarcoma cells under ER stress, P53 directly binds to the promoter of miR-1281, and down-regulates USP39 in osteosarcoma cells through the p5-Mir-1281-USP39 axis, an ERS response pathway, to inhibit and promote cell apoptosis [111]."

sparser
"ERS-induced miR-1281, whose promoter binds to p53 and targets USP39, facilitating the apoptosis of osteosarcoma cells xref ."
TP53 inhibits USP39.
| 1
TP53 inhibits USP39. 1 / 1
| 1

reach
"For instance, USP39 silencing enhanced cisplatin‐induced apoptosis in colon cancer cells by increasing p53 expression [24]."
RBM39 affects USP39
3 | 4
3 | 4

sparser
"Biochemical experiments verify that USP39 and RBM39 interact with each other and highly colocalize in the nucleus."

sparser
"Our proteomics and DUB screening experiments demonstrated that USP39 interacted with RBM39 and upregulated its protein level."

No evidence text available

sparser
"After we demonstrated the interaction between USP39 and RBM39, we sought to test whether and how USP39 regulates RBM39 in gastric cancer cells."

No evidence text available

sparser
"Lu et al. found that USP39 can interact with RBM39 and stabilize it through removal of the polyubiquitin chain by K48 deubiquitination, therefore promoting tumor progression ( xref )."

No evidence text available
GST affects USP39
| 7
| 7

sparser
"The result showed that the K29-linked ubiquitination of Cyclin B1 was significantly reducible after incubated with GST-USP39 protein, suggesting that USP39 directly deubiquitinates Cyclin B1 ( xref d)."

sparser
"Given that GSTUSP39 also exhibited slight binding affinity for other tested ubiquitins, we do not exclude the possibility that USP39 serves as a reader of Lys‐linked chains in cellulo ."

sparser
"The pulldown assay further revealed that GSTUSP39 interacted most strongly with Dap20‐linked diUb, suggesting that USP39 might serve as its reader at least in vitro."

sparser
"The eluate was sequentially incubated with GST-USP39 protein or GST protein followed by detection of K29 linked-CycB1 using anti-HA antibody with Western blotting."

sparser
"To further investigate whether USP39 directly deubiquitinated CHK2, bacterially purified GST-USP39 and ubiquitinated CHK2 proteins were incubated together in a cell-free system."

sparser
"We found that GSTUSP39 did not cleave Dap20‐linked diUb, whereas the pan‐deubiquitinase USP2cc readily cleaved it, suggesting that USP39 did not deubiquitinate at least Dap20‐linked ubiquitin chains (Figure  xref )."

sparser
"To test whether the Cyclin B1-USP39 interaction was direct, we performed GST-pull down assays using GST-USP39 and Flag-CycB1."
Flag affects USP39
| 7
| 7

sparser
"The results indicated that Myc-SP1 was successfully co-immunoprecipitated by Flag-USP39 wild type and mutation type, suggesting an interaction between the two exogenously expressed proteins ( Fig. 4 A[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"The results of Co-IP revealed that Flag-USP39 was significantly enriched in the precipitates of Myc-SIRT7 and vice versa, which indicated that USP39 interacted with SIRT7 in CaSki and SiHa cells (Fig.  xref B)."

sparser
"Flag‐USP33, Flag‐RNF5, Flag‐USP32, and FlagUSP39 were purchased from SinoBiological, and USP33 was then cloned into pCAGGS or pLVX with different tags."

sparser
"We co-expressed Flag-USP39 wild type (WT) and C306A (CA) mutant type (catalytic inactive), and Myc-SP1 constructs in 293 T cells and performed co-IP analysis."

sparser
"HA-ubiquitin and His-PGK1 constructs were co-expressed, with or without Flag-USP39, in Ishikawa and KLE cells."

sparser
"Ectopic expression of Flag-USP39 markedly promoted PGK1 de-ubiquitination (Fig. xref )."

sparser
"To identify whether two proteins are co-localized to the same subcellular compartments, HepG2 cells were immune-stained with Flag-USP39 and Myc-SP1 antibody and visualized by fluorescence microscopy."
Doxycycline affects USP39
| 6
Doxycycline inhibits USP39.
| 3
| 3

reach
"In contrast, luciferase signals were decreased in H1299 cells with USP39 knockdown induced by doxycycline (Fig. 6B)."

reach
"The same number of A549 and H1299 stable cell lines were seeded to 96-well plate (2000 cells per well), and 1 µg/ml doxycycline was added to induce USP39 knockdown in the experimental group."

reach
"Doxycycline (1 µg/ml) was used to induce USP39 knockdown."
Doxycycline activates USP39.
| 3
| 3

reach
"Doxycycline was administered to induce USP39 slicing by oral gavage."

reach
"In addition, we conducted transwell assays to detect cell movement and the results revealed that doxycycline-induced USP39 knockdown drastically suppressed A549 and H1299 cell migration (Fig. S2G, H)."

reach
"USP39 downregulation induced by doxycycline dramatically inhibited the growth of A549 and H1299 cells, as demonstrated by MTT and colony formation assays (Fig. S2C-F)."

reach
"Next, we monitored the effect of the ZF domain in USP39-mediated HR or NHEJ repair."

reach
"Herein, we showed that the iUSP domain is also critical for USP39-mediated HR repair."

reach
"Consistent with previous results, we observed that USP39 depletion reduced both HR and NHEJ repair (Figure 2F)."

reach
"Remarkably, our study implies that USP39 also promotes HR via mechanisms shared with its splicing function."

reach
"In addition, we also found that reintroducing either WT USP39 or the RG/AA mutant rescued USP39 depletion-mediated HR failure, but the RG/AA mutant failed to rescue the NHEJ defect caused by USP39 ablation."

reach
"To rule out that a decrease in transcript levels of USP39-linked factors causes HR or NHEJ defects in USP39 depleted cells, we performed qPCR for USP39-linked HR or NHEJ factors and found that none of the NHEJ factors identified in this study were downregulated by USP39 depletion (Supplementary Figure S13D)."
USP39 affects cell death
| 6
USP39 inhibits cell death.
| 3
| 3

reach
"Depletion of USP39 inhibits cell proliferation and migration and induces cell death in human pancreatic cancer cells."

reach
"Our research demonstrates that USP39 silencing can induce cell death, which is consistent with the reported functions of other deubiquitinase family members such as USP47 [47, 48] and USP7 [49–51] in cell survival regulation."

reach
"Using clonogenic analysis, we also confirmed that the RG/AA mutant failed to rescue USP39 knockdown-mediated cell death (Figure 3J)."
USP39 activates cell death.
| 3
| 3

reach
"Future studies should employ Annexin V/PI double staining flow cytometry to characterize the specific mode of cell death, complemented by Western blot analysis of apoptotic markers such as cleaved PARP and activated Caspase-3, thereby elucidating the molecular pathways involved in USP39-mediated cell death."

reach
"Our results showed that USP39 knockdown reduced the proliferation and migration of pancreatic cancer cells and increased cell death in vitro, suggesting a potential role of USP39 in pancreatic cancer cell growth and survival."

reach
"Knockdown of SF3B1, PRPF8, UBL5 and USP39 increased cell death in all cSCC cell lines."
USP39 affects Wnt
| 5
USP39 activates Wnt. 5 / 6
| 5

reach
"The expression of such markers demonstrated that Usp39 was essential to start the formation of a primitive streak correctly, but dispensable for the formation of a visceral endoderm, including anterior determination.As shown above, considering that USP39 may activate non-canonical Wnt signaling in LM-epidermal cells in vitro (Fig. 3g–p), we examined whether molecular markers for PCP components were affected in Usp39 embryos at E6.5 (Fig. 4l–m′)."

reach
"Taken together, these findings demonstrate that Usp39 genetically interacts with Vangl2 in terms of axial elongation, supporting the notion that USP39 contributes to modulation of non-canonical Wnt signaling.Next, to exclude the possibility of any involvement of USP39 in canonical Wnt signaling, we tested for any genetic interaction between β-catenin and Usp39 (Fig. S9)."

reach
"Therefore, we propose that USP39 can activate non-canonical Wnt signaling partly by allowing GRHL3 to localize in the cytoplasm.This study demonstrates that Usp39 and Grhl3 cooperate to contribute to epithelial morphogenesis during mouse eyelid closure (Figs."

reach
"Here, we prove that USP39 promotes HCC cell proliferation and migration by directly deubiquitin beta-catenin, a key molecular of Wnt/beta-catenin signaling pathway whose abnormal expression or activation results in several tumors, following its co-localization with USP39."

reach
"These findings led us to propose that USP39 contributes to non-canonical Wnt signaling-dependent epithelial morphogenesis by upregulating expression of PCP components including cytoplasmic-localized GRHL3."
USP39 affects VEGFA
| 6
USP39 activates VEGFA.
| 3
USP39 activates VEGFA. 3 / 3
| 3

reach
"USP39 promotes malignant proliferation and angiogenesis of renal cell carcinoma by inhibiting VEGF-A 165b alternative splicing via regulating SRSF1 and SRPK1."

reach
"In renal cancer cells (RCCs), USP39 promotes malignant progression by regulating the anti-angiogenic variant of vascular endothelial growth factor A (VEGF-A), VEGF-A b, in addition to the RNA splicing-related proteins SRSF1 and SRPK1 [90]."

reach
"This potentially originating from the iUSP domain cannot bind ubiquitin either, and the ZnF of USP39 could interact with the splicing independent on ubiquitin [64], which provides the opportunity for SRSF1 binding to USP39 , though further exploration is required to confirm the conclusion.Firstly, one remaining limitation is how USP39 drives the changes in VEGF-A , which needs further research to elucidate the specific mechanisms."
USP39 decreases the amount of VEGFA.
| 2
USP39 decreases the amount of VEGFA. 2 / 2
| 2

reach
"USP39 knockdown upregulated the expression of VEGF-A 165b , and USP39 overexpression downregulated the expression of VEGF-A 165b significantly (both P < 0.05)."

reach
"On the contrary, RCC cells with overexpression of USP39 downregulated the expression of VEGF-A ."
USP39 increases the amount of VEGFA.
| 1
USP39 increases the amount of VEGFA. 1 / 1
| 1

reach
"Knockdown or overexpression of USP39 either upregulates or downregulates VEGF-A 165b expression."
USP39 affects SRSF1
2 | 4
USP39 binds SRSF1.
2 | 3
2 | 3

reach
"This potentially originating from the iUSP domain cannot bind ubiquitin either, and the ZnF of USP39 could interact with the splicing independent on ubiquitin [64], which provides the opportunity for SRSF1 binding to USP39 , though further exploration is required to confirm the conclusion.Firstly, one remaining limitation is how USP39 drives the changes in VEGF-A , which needs further research to elucidate the specific mechanisms."

reach
"The interaction between USP39 and SRPK1/SRSF1 was analyzed by Western blot using anti-Flag tag (Abcam) or anti-SRSF1 (Abcam)."

reach
"The same binding site was found in the interaction between USP39 and SRSF1 (Fig. 5E)."

No evidence text available

No evidence text available
USP39 phosphorylates SRSF1.
| 1
USP39 leads to the phosphorylation of SRSF1. 1 / 1
| 1

reach
"In addition, there was stronger phosphorylation of SRSF1 in 786-O and ACHN cells with overexpression of USP39, and knockdown of USP39 in RCC cells could inhibit phosphorylation of SRSF1 (Fig. 6C, D)."
USP39 affects PFKL
4 | 2
4 | 2

sparser
"The interaction between USP39 and PFKL in liver cancer cells has been confirmed, and the downregulation of USP39 inhibits the increase in PFKL expression caused by DNAAF5 overexpression."

sparser
"In liver cancer cells Hep3B, the interaction between USP39 and PFKL was confirmed, and downregulation of USP39 inhibited the increase in PFKL expression caused by DNAAF5 overexpression."

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP39 affects PDHA1
| 6
USP39 increases the amount of PDHA1.
| 2
USP39 increases the amount of PDHA1. 2 / 2
| 2

reach
"Accordingly, USP39 overexpression was found to elevate PDHA protein levels by about 60% (Fig. 2K)."

reach
"Considering that USP39 silencing reduced PDHA protein levels, we next determined whether USP39 could deubiquitinate PDHA."
USP39 deubiquitinates PDHA1.
| 2
USP39 deubiquitinates PDHA1. 2 / 2
| 2

reach
"Considering that USP39 silencing reduced PDHA protein levels, we next determined whether USP39 could deubiquitinate PDHA."

reach
"The ectopic expression of USP39, under conditions where MG132 was present to prevent proteasomal degradation, led to a more efficient pulldown of PDHA and reduced the level of PDHA ubiquitination (Fig. 2I)."
USP39 decreases the amount of PDHA1.
| 1
USP39 decreases the amount of PDHA1. 1 / 1
| 1

reach
"The ectopic expression of USP39, under conditions where MG132 was present to prevent proteasomal degradation, led to a more efficient pulldown of PDHA and reduced the level of PDHA ubiquitination (Fig. 2I)."
USP39 activates PDHA1.
| 1
USP39 activates PDHA1. 1 / 1
| 1

reach
"Our data show that USP39 promotes PDHA stability through a deubiquitination-mediated process."
USP39 affects H2AB
| 6
USP39 binds H2AB. 6 / 6
| 6

reach
"Isothermal titration calorimetry (ITC) assays further confirmed that Sad1 bound H2AB and H2AZB with comparable dissociation constants (K ) of 9.5 μM and 7.5 μM, respectively (Fig. 1c), indicating that Sad1 does not have a binding preference for H2A or H2A.Z."

reach
"To reveal the structural basis of the interaction between Sad1 and H2AB, we first dissected the structural elements of Sad1 required for the Sad1-H2AB interaction."

reach
"The binding between Sad1 and H2AB is mediated by electrostatic and hydrophobic interactions (Figs."

reach
"The Sad1 F118A mutation destabilized the Sad1-H2AB complex, and the substitution of Sad1 F118 with a positively charged arginine residue (F118R) severely diminished the interaction between Sad1 and H2AB (Fig. 2d)."

reach
"In addition, charge-reverse mutations of D114 and E117 decreased binding affinity between Sad1 and H2AB by 5.6-fold (Fig. 2d)."

reach
"By screening some known silencing factors, our in vitro pull-down assays identified that Clr3 and Sir2 directly interact with the Sad1-H2AB complex (Figs."
| 6
| 6

reach
"Consistently, we observed that the ZF domain is essential for USP39-mediated cell survival, together with the N-terminal RG motifs (Figure 7D)."

reach
"Based on a study conducted by Xing et al., (2018) on colorectal cancer cell lines SW1116 and HCT116, it was found that knockdown of USP39 could inhibit cell viability and colony formation of cell lines significantly in the group of cells treated with USP39 knockdown compared to the negative control group (<0.001)."

reach
"A clonogenic survival assay revealed that cell viability was significantly decreased by USP39 knockdown when compared to that in the siRNA control, and this decrease was dependent on the radiation dose (Figure 2C)."

reach
"Overexpression of USP39 significantly increased the invasion ability and cell survival curve (p < 0.05)."

reach
"Knockdown of USP39 Inhibited HNSCC Cell Viability and Migration."

reach
"The results of the CCK-8 assay showed that USP39 knockdown significantly reduced the cell viability of these HNSCC cells compared with the control group (Figure 4B)."
SRPK1 affects USP39
4 | 1 1
4 | 1 1

No evidence text available

No evidence text available

sparser
"USP39 binds SRPK1 (Serine/arginine-rich splicing factor kinase 1) through its 101–565 fragment, promoting SRPK1-SRSF1 (Serine and arginine-rich splicing factor 1) phosphorylation and interaction, which subsequently regulates VEGF-A165b alternative splicing to drive RCC proliferation and angiogenesis ( xref )."

No evidence text available

reach
"The interaction between USP39 and SRPK1/SRSF1 was analyzed by Western blot using anti-Flag tag (Abcam) or anti-SRSF1 (Abcam)."

No evidence text available
PFKL affects USP39
4 | 2
4 | 2

sparser
"The interaction between USP39 and PFKL in liver cancer cells has been confirmed, and the downregulation of USP39 inhibits the increase in PFKL expression caused by DNAAF5 overexpression."

sparser
"In liver cancer cells Hep3B, the interaction between USP39 and PFKL was confirmed, and downregulation of USP39 inhibited the increase in PFKL expression caused by DNAAF5 overexpression."

No evidence text available

No evidence text available

No evidence text available

No evidence text available
| 5
USP39 inhibits localization.
| 3
| 3

reach
"USP39 Represses the Transcriptional Activity of ETS2 Partly by Suppressing Its Nuclear Localization."

reach
"This indicates that USP39 strongly suppresses the nuclear localization of ETS2."

reach
"USP39-Mediated Non-Proteolytic Control of ETS2 Suppresses Nuclear Localization and Activity."
USP39 activates localization.
| 2
| 2

reach
"Taken together, these findings indicate that USP39 is necessary for the cytoplasmic localization of the Ub-like domain of GRHL3 in RT4 and MCF7 cells."

reach
"Considering that USP39 mediates the cytoplasmic localization of GRHL3, it can be assumed that USP39 expression would be observed during epidermal maturation."
| 1 4
| 1 4

reach
"Third, we demonstrated that USP39 knockdown inhibits cell migration and invasion by upregulating p53 and the downstream proteins MMP2 and MMP9 [XREF_BIBR]."

reach
"In addition, we conducted transwell assays to detect cell movement and the results revealed that doxycycline-induced USP39 knockdown drastically suppressed A549 and H1299 cell migration (Fig. S2G, H)."

eidos
"Third , we demonstrated that USP39 knockdown inhibits cell migration and invasion by upregulating p53 and the downstream proteins MMP2 and MMP9 [ 31 ] ."

reach
"Transwell assay also showed that the enhanced cell migration induced by USP39 overexpression was repressed by GLI1 knockdown (Fig. 6G, H)."

reach
"As shown in XREF_FIG A-F, USP39 knockdown reduced the cell migration and invasion of both USP39KD cells in comparison to the control cells (* p < 0.05, ** p < 0.01, **** p < 0.0001)."
| 5
| 5

reach
"USP39 promotes malignant proliferation and angiogenesis of renal cell carcinoma by inhibiting VEGF-A 165b alternative splicing via regulating SRSF1 and SRPK1."

reach
"USP39 level was higher in hypoxia-induced hRMECs, functionally, USP39 silencing reversed hypoxia-induced migration, invasion and angiogenesis in hRMECs."

reach
"USP39 stabilized SIRT2 expression by deubiquitination and promoted hypoxia-induced metastatic and angiogenic behaviors of RMECs in vitro, as well as retinal angiogenesis in vivo."

reach
"These findings indicated that knockdown or overexpression of USP39 could either inhibit or promote angiogenesis of endothelial cells."

reach
"To explore the potential mechanism of USP39-mediated angiogenesis and malignant proliferation, affinity purification–mass spectrometry (AP-MS) was used to explore the interactions between USP39 and the potential target protein."
USP39 affects PRPF8
5 |
5 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP39 affects PI3K
| 3 2
USP39 phosphorylates PI3K.
| 1 2
USP39 leads to the phosphorylation of PI3K. 3 / 3
| 1 2

sparser
"USP39 efficiently induced the phosphorylation of PI3K and AKT and increased HIF-1α expression in EC cells (Fig. xref )."

sparser
"USP39 effectively induced phosphorylation of PI3 K and AKT and increased the expression of HIF-1α in EC cells."

reach
"USP39 efficiently induced the phosphorylation of PI3K and AKT and increased HIF-1α expression in EC cells (Fig. 7A, B)."
USP39 activates PI3K.
| 2
USP39 activates PI3K. 2 / 2
| 2

reach
"In addition, USP39 silencing blocked the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B pathway (AKT) by regulating SIRT2."

reach
"Collectively, these results indicate that histone lactylation and USP39 promote PI3K/AKT- and HIF-1α-mediated glycolysis in EC cells."
USP39 affects PARP1
| 3 1
USP39 inhibits PARP1.
| 3
USP39 inhibits PARP1. 3 / 4
| 3

reach
"Silencing USP39 expression hinders MGC-803 GC cell proliferation and induces G2/M arrest and PARP cleavage [60]."

reach
"Moreover, depletion of USP39 blocked activation of Akt, mTOR, p53, and PARP signaling pathways."

reach
"USP39 overexpression impedes PARP and Caspase3 activation, diminishing the apoptotic rate in ESCC cells treated with cisplatin [53]."
USP39 binds PARP1.
| 1
| 1

sparser
"Wang et al. found that USP39 can interact with PARP protein, and by knocking down USP39, the cleavage of amino acid 214 of PARP protein was increased, resulting in the loss of PARP protein function and promoting apoptosis in gastric cancer cells ( xref )."
USP39 affects HNRNPC
1 | 3 1
1 | 3 1

sparser
"An additional GST-pulldown assay was conducted to investigate the interaction manner, and the findings indicated a direct interaction between HNRNPC and USP39, while SRSF6 interacted indirectly with USP39 (Fig. xref )."

No evidence text available

reach
"Supporting this, endogenous/ectopically overexpressed USP39 was coimmunoprecipitated with endogenous/ectopic overexpressed HNRNPC protein, suggesting that HNRNPC can interact and help recruit USP39 (Figs."

reach
"Moreover, the Co-IP assay also detected interaction between USP39 and SRSF6/HNRNPC in various mouse cell lines, suggesting this regulatory network is conserved between humans and mice (Fig. 7H)."

reach
"Although a considerable fraction of AS events appear to be species-specific, the interaction between USP39 and SRSF6/HNRNPC is conserved between humans and mice."
USP39 affects ERK
| 4 1
USP39 phosphorylates ERK.
| 1 1
USP39 phosphorylates ERK. 1 / 1
| 1

sparser
"Additionally, USP39 enhanced ERK1/2 phosphorylation, and pharmacological inhibition of ERK1/2 abrogated USP39-driven proliferative and clonogenic capacities."
Modified USP39 leads to the phosphorylation of ERK. 1 / 1
| 1

reach
"Furthermore, the inhibition of USP39 expression decreased the phosphorylation of extracellular signal regulated kinase (ERK) 1/2, indicating that ERK signaling pathways might be involved in the regulation of melanoma cell proliferation by USP39."
USP39 activates ERK.
| 2
USP39 activates ERK. 2 / 2
| 2

reach
"Similarly, USP39 promotes malignant melanoma progression by regulating ERK signaling [56]."

reach
"Xu et al. reported that the knockdown of USP39 increased the levels of apoptosis-related proteins, such as caspase-3, caspase-8, caspase-9, and PARP, in RCCs, and inhibited the activation of ERK and AKT signaling pathways, resulting in an increase in the apoptosis rate of cancer cells [55]."
USP39 inhibits ERK.
| 1
USP39 inhibits ERK. 1 / 1
| 1

reach
"Mechanistically, downregulation of USP39 blocked the activation of Akt and extracellular signal regulated kinase signaling pathways in RCC cells."
USP39 affects EFTUD2
5 |
5 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP39 affects Cebpb
1 | 4
1 | 4

sparser
"These constructs, along with full-length SFB-USP39, were co-transfected into HEK293T cells, and SFB-USP39 was pulled down using S-protein agarose beads. xref B shows that both full-length ETS2 and three ETS2 mutants, but not 171–362, interacted with USP39."

sparser
"Then, we examined the interaction of SFB-USP39 with these immunoprecipitated proteins."

No evidence text available

sparser
"To investigate this, we co-transfected MYC-ETS2 with SFB-USP39 or SFB-GFP plasmids into HEK293T cells and separated the cytoplasmic and nuclear fractions of the cell lysates."

sparser
"To do so, we co-transfected the ETS2-responsive reporter plasmid with MYC-ETS2 alone, SFB-USP39 alone, or both plasmids into HEK293T cells."

reach
"It has been reported that USP39 promoted the growth of human hepatocellular carcinoma in vitro and in vivo ( Yuan et al., 2015 )."

reach
"In particular, USP39 de-ubiquitinates and stabilizes CHK2 to regulate the DNA damage response and chemical radiation resistance [43], de-ubiquitinates and stabilizes the SP1 protein to promote hepatocellular carcinoma progression [44], and inhibits VEGF-A165b-selective splicing by regulating SRSF1 and SRPK1 to promote malignant proliferation and angiogenesis of renal cell carcinoma [45]."

reach
"USP39/SMC4 promotes hepatoma cell proliferation and 5-FU resistance."
USP39 affects CDKN1A
| 5
USP39 inhibits CDKN1A.
| 4
USP39 inhibits CDKN1A. 4 / 4
| 4

reach
"Its level is negatively correlated with that of USP39, and knockdown of USP39 prolongs the half-life of p21 and induces apoptosis in colon cancer cell lines[41]."

reach
"However, treated with PFT-alpha reduced the up-regulation of p21 and BAX induced by USP39 knockdown, but had no effect on the down-regulation of cell cycle related proteins (CDK1 and CyclinB1 and CDK2 and CyclinA2) induced by USP39 knockdown."

reach
"Meanwhile, we found that USP39 knockdown also activates the p53 pathway, upregulation of p53, p-p53 (S15), p21 and BAX in HCC827 cells."

reach
"USP39 down-regulates the p53/p21 signaling pathway and stabilizes CDK1 and cyclin B1 to promote the proliferation of ovarian cancer cells [34]."
USP39 decreases the amount of CDKN1A.
| 1
USP39 decreases the amount of CDKN1A. 1 / 1
| 1

reach
"Furthermore, silencing of USP39, a target of miR-1281 in human osteosarcoma cells, inhibits survival under endoplasmic reticulum stress and slows the metastasis of malignant bone tumors to other tissues and organs by increasing the expression of Cyclin A2 and p21, leading to cell cycle arrest in the G2/M phase and promoting apoptosis [43, 92, 93]."
USP39 affects CD2BP2
5 |
5 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP39 affects BRCA1
| 5
USP39 increases the amount of BRCA1.
| 3
USP39 increases the amount of BRCA1. 3 / 3
| 3

reach
"Although, how USP39 modulates BRCA1 mRNA expression as a spliceosome component remains unclear, it is clear that it is not linked to the PAR-dependent USP39 function in DDR."

reach
"Interestingly, similar to our results, they also found that the level of BRCA1 mRNA is significantly decreased by USP39 depletion (74)."

reach
"In parallel, we have also shown that USP39 depletion leads to decreased mRNA expression of BRCA1, which might affect the BRCA1 foci formation."
USP39 activates BRCA1.
| 2
USP39 activates BRCA1. 2 / 2
| 2

reach
"Although the aforementioned study showing the DUB activity of USP39 is controversial compared to that in previous studies (59,60), it is possible that USP39 modulates BRCA1-coupled HR in a PAR-independent fashion in various ways.Lastly, a recent study showed that the recruitment of 53BP1 to DNA lesions was not impaired after PARP inhibition (91)."

reach
"However, we found that BRCA1 mRNA was significantly reduced by USP39 depletion."
USP39 affects ADAM9
| 3 2
USP39 binds ADAM9.
| 2
| 2

sparser
"Furthermore, to determine whether USP39 could interact with ADAM9 and regulate the ubiquitination of ADAM9, we co‐transfected Myc‐tagged USP39, Flag‐tagged ADAM9 with or without HA tagged Ub plasmids into HEK293T cells; co‐immunoprecipitation experiments revealed that USP39 failed to interact with ADAM9 at the protein level (Fig.  xref ) and overexpressing USP39 had no effect on the polyubiquitination of ADAM9 (Fig. S9B)."

sparser
"Interestingly, Xiao et al. found that USP39 also directly binds to ADAM9 mRNA and promotes its pre-mRNA maturation, thereby altering the expression and activity of integrin β1 and promoting migration and invasion of human glioma cells ( xref )."
USP39 activates ADAM9.
| 2
USP39 activates ADAM9. 2 / 2
| 2

reach
"The similar mechanism of USP39 was also found in human glioma in which USP39 could induce ADAM9 mRNA maturation but not protein to promote glioma progression [53]."

reach
"Further on, USP39 induced ADAM9 mRNA maturation and decreased the expression of integrin beta1."
USP39 increases the amount of ADAM9.
| 1
USP39 increases the amount of ADAM9. 1 / 1
| 1

reach
"Altogether, our data shows that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered as potential target for treating patients with glioma."
STAT1 affects USP39
1 | 2 2
STAT1 binds USP39.
1 | 1 2
1 | 1 2

sparser
"Furthermore, USP39 interacts with STAT1 and removes K6-linked ubiquitin chains, thereby stabilizing the STAT1 protein ( xref )."

reach
"A recent report describes how USP39 is able to bind nuclear-localized STAT1 and sustain the STAT1 protein level by deubiquitination; consequently, this is a means to export deubiquitinated STAT1 from the nucleus to the cytoplasm by avoiding its degradation ."

sparser
"In the host antiviral defense mechanism, USP39 interacts with STAT1, resulting in a notable reduction in the ubiquitination of the K6-linkage, but not the K48-linkage, of STAT1."

No evidence text available
STAT1 inhibits USP39.
| 1
STAT1 inhibits USP39. 1 / 1
| 1

reach
"When we knocked down USP39, STAT1 expression was also decreased."
SRSF6 affects USP39
| 4 1
SRSF6 binds USP39.
| 3 1
| 3 1

reach
"Moreover, the Co-IP assay also detected interaction between USP39 and SRSF6/HNRNPC in various mouse cell lines, suggesting this regulatory network is conserved between humans and mice (Fig. 7H)."

sparser
"An additional GST-pulldown assay was conducted to investigate the interaction manner, and the findings indicated a direct interaction between HNRNPC and USP39, while SRSF6 interacted indirectly with USP39 (Fig. xref )."

reach
"Although a considerable fraction of AS events appear to be species-specific, the interaction between USP39 and SRSF6/HNRNPC is conserved between humans and mice."

reach
"This binding between SRSF6 and USP39 aids the recruitment of USP39 to the SRSF6-binding motif-enriched region."
SRSF6 activates USP39.
| 1
SRSF6 bound to USP39 activates USP39. 1 / 1
| 1

reach
"This binding between SRSF6 and USP39 aids the recruitment of USP39 to the SRSF6-binding motif-enriched region."
SRSF1 affects USP39
2 | 3
2 | 3

reach
"This potentially originating from the iUSP domain cannot bind ubiquitin either, and the ZnF of USP39 could interact with the splicing independent on ubiquitin [64], which provides the opportunity for SRSF1 binding to USP39 , though further exploration is required to confirm the conclusion.Firstly, one remaining limitation is how USP39 drives the changes in VEGF-A , which needs further research to elucidate the specific mechanisms."

reach
"The interaction between USP39 and SRPK1/SRSF1 was analyzed by Western blot using anti-Flag tag (Abcam) or anti-SRSF1 (Abcam)."

reach
"The same binding site was found in the interaction between USP39 and SRSF1 (Fig. 5E)."

No evidence text available

No evidence text available
PRPF8 affects USP39
5 |
5 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
KAT8 affects USP39
2 | 3
KAT8 acetylates USP39.
| 3
KAT8 acetylates USP39. 3 / 3
| 3

sparser
"Previously, it was reported that USP39 could be acetylated by histone acetyltransferase MYST1, and the acetylated USP39 was subsequently degraded by E3 ubiquitin ligase VHL-mediated proteasomal degradation."

sparser
"A study has demonstrated that USP39 can be acetylated by the histone acetyltransferase MYST1, which leads to its degradation by the proteasome."

sparser
"USP39 can be acetylated by the acetyltransferases HAT and MYST1."
KAT8 binds USP39.
2 |
2 |

No evidence text available

No evidence text available
HNRNPC affects USP39
1 | 3 1
1 | 3 1

sparser
"An additional GST-pulldown assay was conducted to investigate the interaction manner, and the findings indicated a direct interaction between HNRNPC and USP39, while SRSF6 interacted indirectly with USP39 (Fig. xref )."

No evidence text available

reach
"Supporting this, endogenous/ectopically overexpressed USP39 was coimmunoprecipitated with endogenous/ectopic overexpressed HNRNPC protein, suggesting that HNRNPC can interact and help recruit USP39 (Figs."

reach
"Moreover, the Co-IP assay also detected interaction between USP39 and SRSF6/HNRNPC in various mouse cell lines, suggesting this regulatory network is conserved between humans and mice (Fig. 7H)."

reach
"Although a considerable fraction of AS events appear to be species-specific, the interaction between USP39 and SRSF6/HNRNPC is conserved between humans and mice."
EFTUD2 affects USP39
5 |
5 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available
Cebpb affects USP39
1 | 4
1 | 4

sparser
"These constructs, along with full-length SFB-USP39, were co-transfected into HEK293T cells, and SFB-USP39 was pulled down using S-protein agarose beads. xref B shows that both full-length ETS2 and three ETS2 mutants, but not 171–362, interacted with USP39."

sparser
"Then, we examined the interaction of SFB-USP39 with these immunoprecipitated proteins."

No evidence text available

sparser
"To investigate this, we co-transfected MYC-ETS2 with SFB-USP39 or SFB-GFP plasmids into HEK293T cells and separated the cytoplasmic and nuclear fractions of the cell lysates."

sparser
"To do so, we co-transfected the ETS2-responsive reporter plasmid with MYC-ETS2 alone, SFB-USP39 alone, or both plasmids into HEK293T cells."
CTNNB1 affects USP39
2 | 3
2 | 3

sparser
"Co-immunoprecipitation and ubiquitination assays were performed to confirm the interaction between USP39 and β-catenin."

sparser
"These observations suggested that deubiquitinase USP39 interacts with β-catenin to inhibit the HCC cell proliferation."

No evidence text available

sparser
"Next, to exclude the possibility of any involvement of USP39 in canonical Wnt signaling, we tested for any genetic interaction between β-catenin and Usp39 (Fig. S xref )."

No evidence text available
CD2BP2 affects USP39
5 |
5 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available

No evidence text available

sparser
"Inhibition of USP39 by siRNA has downregulated FOXM1 and in turn led to tumor volume reduction in xenograft model of HCC ( xref )."

sparser
"Furthermore, inhibition of USP39 by siRNA resulted in a diminished clonogenic capacity in both cell lines, with the proteasome inhibitor BTZ serving as a positive control for inhibition of clonogenic potential (Fig.  xref C-D)."

sparser
"Conversely, inhibition of USP39 by siRNA accelerated the degradation of ZEB1 induced by CHX (Fig.  xref D and Fig. S6B)."

sparser
"Specific inhibition of USP39 by these siRNAs led to a significant reduction in USP39 expression, accompanied by a substantial induction of cell death and a marked decrease in cellular metabolism in both OPM2 and KMM1 cells after 96 h (Fig.  xref A-B)."
Rep affects USP39
4 |
4 |

No evidence text available
| DOI

No evidence text available

No evidence text available

No evidence text available

reach
"In addition, USP39 downregulation could inhibit the EMT phenotype in HCC cells (Fig. 3C)."

reach
"The zinc finger E-box binding homology cassette (ZEB1) is a key inducer of epithelial–mesenchymal transition (EMT), promoting cancer cell metastasis; USP39 inhibits the degradation of ZEB1 and promotes the development of EMT through deubiquitylation, further accelerating the invasion and metastasis of HCC cells [38]."

reach
"USP17 and USP39 stimulate EMT in ovarian cancer cells and, thus, their ability to migrate [86,87] ."

reach
"Our previous studies have shown that overexpressed USP39 can promote the proliferation and migration of human ovarian cancer by targeting EMT [15]."

reach
"In parallel, we examined whether the ZF domain is important for USP39-mediated NHEJ repair or cell survival."

reach
"USP39 directly drives XRCC4/LIG4 dependent NHEJ repair."

reach
"Consistent with previous results, we observed that USP39 depletion reduced both HR and NHEJ repair (Figure 2F)."

reach
"In addition, we also found that reintroducing either WT USP39 or the RG/AA mutant rescued USP39 depletion-mediated HR failure, but the RG/AA mutant failed to rescue the NHEJ defect caused by USP39 ablation."
USP39 affects USP39
| 3
USP39 increases the amount of USP39.
| 1
USP39 increases the amount of USP39. 1 / 2
| 1

reach
"Overexpressing USP39 substantially increased total USP39 levels, including endogenous and overexpressed USP39, in both the cytoplasm and nucleus."
USP39 activates USP39.
| 1
USP39 activates USP39. 1 / 1
| 1

reach
"Indeed, silencing USP39 expression markedly inhibited the proliferation and metastasis of HCC cells in vitro and in vivo experiments, indicating the potential carcinogenic effect of USP39 in HCC development."
USP39 acetylates USP39.
| 1
USP39 leads to the acetylation of USP39. 1 / 1
| 1

reach
"Further analysis revealed that USP39 acetylation was inhibited by wild type SIRT7, and the mutant SIRT7 without USP39 acetylation activity (SIRT7 H187Y) was demonstrated to suppress USP39 deacetylation (Fig. 3E)."
USP39 affects Thr-Thr
| 4
USP39 inhibits Thr-Thr.
| 2
| 2

reach
"Knockdown of USP39 significantly inhibited proliferation of TT cells in vitro."

reach
"This indicates that USP39 shRNA could strongly block (p < 0.01) the cell cycle progression of TT cells."
USP39 activates Thr-Thr.
| 2
USP39 activates Thr-Thr. 2 / 2
| 2

reach
"This indicates that knockdown of USP39 could strongly decrease the proliferation of TT cells."

reach
"Taken together, these results suggest that knockdown of USP39 could inhibit TT cell proliferation by inducing G2/M phase cell cycle arrest."
USP39 affects SRSF6
| 3 1
| 3 1

reach
"Moreover, the Co-IP assay also detected interaction between USP39 and SRSF6/HNRNPC in various mouse cell lines, suggesting this regulatory network is conserved between humans and mice (Fig. 7H)."

sparser
"An additional GST-pulldown assay was conducted to investigate the interaction manner, and the findings indicated a direct interaction between HNRNPC and USP39, while SRSF6 interacted indirectly with USP39 (Fig. xref )."

reach
"Although a considerable fraction of AS events appear to be species-specific, the interaction between USP39 and SRSF6/HNRNPC is conserved between humans and mice."

reach
"This binding between SRSF6 and USP39 aids the recruitment of USP39 to the SRSF6-binding motif-enriched region."
USP39 affects SNRNP40
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
USP39 affects SNRNP200
1 | 3
USP39 inhibits SNRNP200.
| 3
| 3

reach
"In the splicing reaction, on the other hand, Sad1 could potentially directly or indirectly suppress the activity of Brr2."

reach
"In contrast, human Brr2 is held in an unengaged position in the tri-snRNP by Sad1, which may repress premature Brr2 unwinding of U4/U6 interactions [ 5 •• ] ( Figure 1 )."

reach
"In the human tri-snRNP assembly, SNRNP200 is sequestered by hSad1 ( USP39 ) in a preactivation position close to Prpf8 RT domain and Prpf6 [21] ."
USP39 binds SNRNP200.
1 |

No evidence text available
USP39 affects SMC4
| 2 2
| 2 2

reach
"Further, we used the co-immunoprecipitation analysis to investigate the interaction between USP39 and SMC4, as well as the ubiquitination status of SMC4 (Fig. 3B)."

sparser
"The results revealing a binding interaction between USP39 and SMC4, with a significant reduction in SMC4 protein levels in the USP39-siRNA group compared to the control groups."

reach
"The results revealing a binding interaction between USP39 and SMC4, with a significant reduction in SMC4 protein levels in the USP39-siRNA group compared to the control groups."

sparser
"Further, we used the co-immunoprecipitation analysis to investigate the interaction between USP39 and SMC4, as well as the ubiquitination status of SMC4 (Fig.  xref B)."
USP39 affects PRPF6
3 | 1
USP39 binds PRPF6.
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 activates PRPF6.
| 1
USP39 activates PRPF6. 1 / 1
| 1

reach
"The subsequent association of the U4/U6 di-snRNP proteins and USP39 could promote the stable association of the PRP6 N-terminal regions along PRP8 , PRP8 α-helical bundle (PRP8 ), and PRP8 domains (Extended Data Fig. 4f)."
USP39 affects PRPF4
1 3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 binds PRPF4 bound to SART1, SNRNP200, PRPF6, LSM8, SNRPA, SNRPB, SNU13, SNRPE, SNRPF, SNRPG, LSM3, LSM6, SNRPD1, SNRPD2, SNRPD3, TXNL4A, EFTUD2, USP39, PRPF8, SNRNP27, PRPF31, SNRNP40, RBM42, DDX23, LSM7, LSM2, LSM5, and LSM4. 1 / 1
1 |

"The major spliceosomal building blocks are the U1, U2, U4/U6, and U5 small nuclear ribonucleoproteins (snRNPs). Each consists of a small nuclear RNA (snRNA) (or two, in the case of U4/U6), seven Sm proteins that form a ring (or seven Lsm proteins in the case of U6), and a variable number of snRNP-specific proteins (Fig. 1F) (Will and Lührmann 2011). Under splicing conditions, the U4/U6 and U5 snRNPs form a 25S U4/U6.U5 tri-snRNP, in which the U4 and U6 snRNAs are base-paired, forming a three-way junction."
USP39 affects NFKBIA
2 | 2
2 | 2

sparser
"IκBα has been shown to be a negative regulator in the inflammatory response to NF-κB, and USP39 binds to IκBα preventing IκBα degradation by removing the ubiquitin chain of IκBα at Lys48-linked ubiquitination to inhibit inflammation occurrence ( xref )."

sparser
"In the inflammatory response, USP39 interacts with IκBα, stabilizing basal levels of IκBα by reducing K48-linked polyubiquitination on IκBα."

No evidence text available

No evidence text available
USP39 affects FlaG
| 4
| 4

sparser
"To provide further evidence for the direct binding of Usp39 to Hsf1 , we performed a RIP assay in AML12 cells overexpressing FLAG-Usp39."

sparser
"Hemagglutinin (HA) tagged RBM39 (HA-RBM39) was detected in the immunoprecipitate of FLAG-USP39 ( xref A ) and HA-USP39 was also observed in the reverse immunoprecipitation of FLAG-RBM39 ( xref B ), indicating their interaction in the overexpressed system."

sparser
"Second, we expressed either FLAG-USP39 or HA-RBM39 in HEK293T cells and immunoprecipitated them with anti-FLAG affinity gel or anti-HA magnetic beads."

sparser
"Immunofluorescence results clearly demonstrated that FLAG-USP39 (green) and HA-RBM39 (red) overexpressed in HEK293 cells were indeed remarkably colocalized in the nucleus with a high Pearson’s correlation coefficient of 0.93 ( xref G )."
USP39 affects E protein
| 4
USP39 deubiquitinates E protein.
| 3
USP39 deubiquitinates E protein. 3 / 3
| 3

reach
"Furthermore, USP39 silencing had no effect on the replication of SARS-CoV-2 in the RNF5 KO cells compared with that in the wild-type cells ( Fig. 8 B–D), suggesting that USP39 specifically reverses po[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Here, we report that USP39 facilitates viral replication by deubiquitinating SARS-CoV-2 E protein and preventing it degradation from the E3 ligase RNF5.Thirteen percent of DUBs have been predicted to [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"These results suggest that USP39 decreases the ubiquitination of the E protein and enhances its stability.We next examined the co-localization of USP39 or USP14 with the E protein and RNF5."
USP39 binds E protein.
| 1
USP39 binds E protein. 1 / 1
| 1

reach
"Moreover, the interaction of USP39 and the E protein was readily detectable in reciprocal co-immunoprecipitation (co-IP) experiments ( Fig. 3 B and C)."

reach
"When the two plasmids were co-expressed, USP39 significantly suppressed the transcription driven by ETS2."

reach
"USP39 suppressed the transcription activity of ETS2 by approximately 72.8%, while OTUD7A and OTUD7B increased the transcription activity of ETS2 by approximately 55.2% and 68.5%, respectively."

reach
"The results demonstrated that the level of the 3 '-end of EGFR decreased (P = 0.0015) more sharply than that of the 5 '-end (P = 0.0069), and the ratio ofthe 3 '-end to 5 '-end levels was significant decreased (P = 0.0297), implying that knockdown of USP39 might inhibit the transcription elongation of EGFR, and might produce unstable EGFR mRNA fragments lacking the 3 '-UTR."

reach
"In addition, USP39 overexpression could promote SRPK1 phosphorylation of SRSF1, while knockdown of USP39 worked oppositely, confirming that USP39 and SRPK1 play a role through direct binding rather than affecting their transcription or translation."
USP39 affects DDX23
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
SNRNP40 affects USP39
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
SMC4 affects USP39
| 2 2
| 2 2

reach
"Further, we used the co-immunoprecipitation analysis to investigate the interaction between USP39 and SMC4, as well as the ubiquitination status of SMC4 (Fig. 3B)."

sparser
"The results revealing a binding interaction between USP39 and SMC4, with a significant reduction in SMC4 protein levels in the USP39-siRNA group compared to the control groups."

reach
"The results revealing a binding interaction between USP39 and SMC4, with a significant reduction in SMC4 protein levels in the USP39-siRNA group compared to the control groups."

sparser
"Further, we used the co-immunoprecipitation analysis to investigate the interaction between USP39 and SMC4, as well as the ubiquitination status of SMC4 (Fig.  xref B)."
PRPF4 affects USP39
1 3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 binds PRPF4 bound to SART1, SNRNP200, PRPF6, LSM8, SNRPA, SNRPB, SNU13, SNRPE, SNRPF, SNRPG, LSM3, LSM6, SNRPD1, SNRPD2, SNRPD3, TXNL4A, EFTUD2, USP39, PRPF8, SNRNP27, PRPF31, SNRNP40, RBM42, DDX23, LSM7, LSM2, LSM5, and LSM4. 1 / 1
1 |

"The major spliceosomal building blocks are the U1, U2, U4/U6, and U5 small nuclear ribonucleoproteins (snRNPs). Each consists of a small nuclear RNA (snRNA) (or two, in the case of U4/U6), seven Sm proteins that form a ring (or seven Lsm proteins in the case of U6), and a variable number of snRNP-specific proteins (Fig. 1F) (Will and Lührmann 2011). Under splicing conditions, the U4/U6 and U5 snRNPs form a 25S U4/U6.U5 tri-snRNP, in which the U4 and U6 snRNAs are base-paired, forming a three-way junction."
NFKBIA affects USP39
2 | 2
2 | 2

sparser
"IκBα has been shown to be a negative regulator in the inflammatory response to NF-κB, and USP39 binds to IκBα preventing IκBα degradation by removing the ubiquitin chain of IκBα at Lys48-linked ubiquitination to inhibit inflammation occurrence ( xref )."

sparser
"In the inflammatory response, USP39 interacts with IκBα, stabilizing basal levels of IκBα by reducing K48-linked polyubiquitination on IκBα."

No evidence text available

No evidence text available
FlaG affects USP39
| 4
| 4

sparser
"To provide further evidence for the direct binding of Usp39 to Hsf1 , we performed a RIP assay in AML12 cells overexpressing FLAG-Usp39."

sparser
"Hemagglutinin (HA) tagged RBM39 (HA-RBM39) was detected in the immunoprecipitate of FLAG-USP39 ( xref A ) and HA-USP39 was also observed in the reverse immunoprecipitation of FLAG-RBM39 ( xref B ), indicating their interaction in the overexpressed system."

sparser
"Second, we expressed either FLAG-USP39 or HA-RBM39 in HEK293T cells and immunoprecipitated them with anti-FLAG affinity gel or anti-HA magnetic beads."

sparser
"Immunofluorescence results clearly demonstrated that FLAG-USP39 (green) and HA-RBM39 (red) overexpressed in HEK293 cells were indeed remarkably colocalized in the nucleus with a high Pearson’s correlation coefficient of 0.93 ( xref G )."
DDX23 affects USP39
4 |
4 |

No evidence text available

No evidence text available

No evidence text available

No evidence text available
ZRANB1 affects USP39
1 | 1 1
1 | 1 1

No evidence text available

reach
"For example, the interaction between ZRANB2 and USP39, annotated by IntAct and BioGRID, is not correct because the cited article shows instead the interaction between ZRANB1 and USP39."

sparser
"For example, the interaction between ZRANB2 and USP39, annotated by IntAct and BioGRID, is not correct because the cited article ( xref ) shows instead the interaction between ZRANB1 and USP39."
ZEB1 affects USP39
| 3
| 3

sparser
"Co-immunoprecipitation assays demonstrated the formation of a complex between endogenous USP39 and ZEB1 proteins in OPM2 cells (Fig.  xref F)."

sparser
"It was previously reported that USP5 promotes HCC progression by stabilizing SLUG xref , while USP39 interacts with ZEB1 and regulates HCC proliferation xref ."

sparser
"To elucidate whether USP39 modulates the ubiquitination status of ZEB1, we initially examined the interaction between the USP39 enzyme and its substrate ZEB1."

reach
"USP39 knockdown inhibits clonogenic capacity, induces cell cycle arrest, triggers apoptosis, and overcomes BTZ resistance."

reach
"Knockdown of USP39 can promote apoptosis and cell cycle arrest in HCC cells, and SP1 reverses these effects (26)."

reach
"Our previous studies have established that USP39 knockdown induces cell cycle arrest at the G2/M phase in non-small cell lung cancer (NSCLC) and colorectal cancer cells, subsequently triggering apoptosis through activation of the p53 pathway [40, 41]."
USP39 affects ZRANB1
1 | 1 1
1 | 1 1

No evidence text available

reach
"For example, the interaction between ZRANB2 and USP39, annotated by IntAct and BioGRID, is not correct because the cited article shows instead the interaction between ZRANB1 and USP39."

sparser
"For example, the interaction between ZRANB2 and USP39, annotated by IntAct and BioGRID, is not correct because the cited article ( xref ) shows instead the interaction between ZRANB1 and USP39."
USP39 affects SART1
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 affects SARS-CoV-2
| 3
| 3

reach
"These results suggest that USP39 promotes the replication of SARS-CoV-2 possibly by stabilizing the E protein.To exclude the other roles of USP39 during SARS-CoV-2 infection, the effect of USP39 on ot[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"In contrast, the knockdown of endogenous USP39 restricted the viral mRNA, viral titers in culture supernatant and protein levels of both the SARS-CoV-2 Omicron ( Fig. 7 G–I) and Delta strains ( Fig. 7[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Chen et al. recently reported that USP39 enhances SARS-CoV-2 replication by deubiquitinating and stabilizing the envelope protein of this virus."
USP39 affects RB1
| 3
USP39 activates RB1. 3 / 3
| 3

reach
"It showed that the down-regulation of USP39 gene can cause rb1 mRNA splicing abnormalities, which then leaded to downstream target genes e2f4 up-regulated in zebrafish."

reach
"Our studies reveal a novel role of usp39 mediated mRNA splicing of rb1 in pituitary cell growth control, which is critical for maintaining embryonic pituitary homeostasis."

reach
"We then performed an rb1 mRNA overexpression experiment in usp39 mutants and observed partial rescue of the adenohypophysis phenotype (XREF_FIG, mutant N = 34, ~ 50% showed rescue), validating the importance of usp39 mediated rb1 mRNA splicing in controlling pituitary lineage expansion during development."
USP39 affects PRPF3
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 affects PRP4K
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 affects M
2 1 |
M binds USP39. 3 / 3
2 1 |

No evidence text available

No evidence text available
| DOI

No evidence text available
USP39 affects Interferon
| 3
| 3

reach
"Mechanistically, USP39 does not affect the production of type I IFN but significantly promotes JAK and STAT downstream of type I signaling by enhancing IFN stimulated response elements promoter activity and expression of IFN stimulated genes."

reach
"Intriguingly, USP39 promotes IFN-mediated antiviral responses by decreasing K6-linked but not canonical K48-linked polyubiquitination of STAT1 for degradation (118), eventhough K6-linked ubiquitin chains are often related to DNA damage instead of protein degradation (142)."

reach
"Unlike USP2A, the deubiquitinating enzymes BRCC36, USP13, and USP39 positively regulate IFN activities by attenuating the polyubiquitination level of STAT1, and this process is independent of IFN treatment, which suggests divergent functional roles of these DUBs under differential contexts.Additionally, ATXN3 does not affect IFN-I production during viral infection but positively regulates IFNAR1-mediated downstream signaling by targeting HDAC3 (108)."
USP39 affects HNRNPU
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
USP39 affects HMGA2
| 1 2
| 1 2

reach
"Consistent with this, USP39 bound to biotin labeled HMGA2 in an RNA pull-down assay, indicating a direct interaction between USP39 and HMGA2."

sparser
"Consistent with this, USP39 bound to biotin-labeled HMGA2 in an RNA pull-down assay (Fig. xref ), indicating a direct interaction between USP39 and HMGA2."

sparser
"We next investigated the functional significance of the USP39-HMGA2 axis."
USP39 affects HDACs
| 3
USP39 binds HDACs. 3 / 3
| 3

reach
"These data suggest that H2A-H2B could enhance the interaction between Sad1 and HDACs, including Sir2 and Clr3.To further support the role of Sad1 in recruiting HDACs, we used ChIP-qPCR assay to examine how Sad1 affects the enrichment of Sir2 in telomere regions."

reach
"These results collectively suggest that the Sad1-H2AB interaction cooperatively enhances the interaction between Sad1 and HDACs, which facilitates the recruitment of HDACs to heterochromatin to ensure the correct epigenetic status required for heterochromatin silencing."

reach
"Mechanistically, H2A-H2B enhances the interaction between Sad1 and HDACs, including Clr3 and Sir2, to maintain epigenetic identity of heterochromatin."
USP39 affects H2AC20
| 3
| 3

reach
"The interaction between Sad1 and H2A-H2B was also held when the GST pull-down assay was performed using a single-chain fusion of H2A and H2B (hereafter referred to as H2AB) (Supplementary Fig. 1b), which has been shown to be structurally similar to the wild type H2A-H2B heterodimer ."

reach
"Our results revealed a nucleosome-independent function of H2A-H2B: H2A-H2B physically associates with Sad1 to regulate Sad1’s interaction with other factors, such as Sir2 and Clr3, and promote the LLPS ability of Sad1."

reach
"We solved the crystal structure of the histone binding motif (HBM) of Sad1 in a complex with a H2A-H2B fusion protein and showed that the DEF/Y motif of Sad1 binds H2A-H2B."

reach
"Using CCK8, EdU, and colony formation assays, as well as in vivo trials, USP39 was shown to promote EC proliferation and migration."

reach
"Collectively, these results indicate that histone lactylation and USP39 promote PI3K/AKT- and HIF-1α-mediated glycolysis in EC cells."

reach
"Histone lactylation and USP39 promote EC development, and USP39 overexpression reverses the suppression of tumor growth by 2-DG in vivo."
USP39 affects CDK4
| 3
USP39 decreases the amount of CDK4.
| 2
USP39 decreases the amount of CDK4. 2 / 2
| 2

reach
"Knockdown of USP39 inhibits VSMC proliferation and the expression of cyclin D1 and CDK4."

reach
"Knockdown of USP39 in VSMCs inhibited cyclinD1 and CDK4 protein expression compared with transfection with control siRNA (XREF_FIG), which are essential proteins for G1/S phase transformation."
USP39 increases the amount of CDK4.
| 1
USP39 increases the amount of CDK4. 1 / 1
| 1

reach
"Furthermore, knockdown of USP39 inhibited VSMC cell proliferation and the expression of cyclin D1 and cyclin dependent kinase 4, as analyzed via cell counting, MTT assay and western blotting."
SART1 affects USP39
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
PRPF6 affects USP39
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
PRPF3 affects USP39
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
PRP4K affects USP39
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
M affects USP39
2 1 |
M binds USP39. 3 / 3
2 1 |

No evidence text available

No evidence text available
| DOI

No evidence text available
HNRNPU affects USP39
3 |
3 |

No evidence text available

No evidence text available

No evidence text available
HMGA2 affects USP39
| 1 2
| 1 2

reach
"Consistent with this, USP39 bound to biotin labeled HMGA2 in an RNA pull-down assay, indicating a direct interaction between USP39 and HMGA2."

sparser
"Consistent with this, USP39 bound to biotin-labeled HMGA2 in an RNA pull-down assay (Fig. xref ), indicating a direct interaction between USP39 and HMGA2."

sparser
"We next investigated the functional significance of the USP39-HMGA2 axis."
HDACs affects USP39
| 3
USP39 binds HDACs. 3 / 3
| 3

reach
"These data suggest that H2A-H2B could enhance the interaction between Sad1 and HDACs, including Sir2 and Clr3.To further support the role of Sad1 in recruiting HDACs, we used ChIP-qPCR assay to examine how Sad1 affects the enrichment of Sir2 in telomere regions."

reach
"These results collectively suggest that the Sad1-H2AB interaction cooperatively enhances the interaction between Sad1 and HDACs, which facilitates the recruitment of HDACs to heterochromatin to ensure the correct epigenetic status required for heterochromatin silencing."

reach
"Mechanistically, H2A-H2B enhances the interaction between Sad1 and HDACs, including Clr3 and Sir2, to maintain epigenetic identity of heterochromatin."
E protein affects USP39
| 3
E protein inhibits USP39.
| 2
E protein inhibits USP39. 2 / 2
| 2

reach
"These results suggest that USP39 decreases the ubiquitination of the E protein and enhances its stability.We next examined the co-localization of USP39 or USP14 with the E protein and RNF5."

reach
"These results support our hypothesis that SARS-CoV-2 utilizes the deubiquitinating ability of USP39 to protect E from degradation by the restrictive factor RNF5.As an important structural protein of S[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
E protein binds USP39.
| 1
USP39 binds E protein. 1 / 1
| 1

reach
"Moreover, the interaction of USP39 and the E protein was readily detectable in reciprocal co-immunoprecipitation (co-IP) experiments ( Fig. 3 B and C)."
Tetrachloromethane increases the amount of USP39. 2 / 2
2 |

No evidence text available

No evidence text available
2 |
Sodium arsenite increases the amount of USP39.
1 |
Sodium arsenite increases the amount of USP39. 1 / 1
1 |

No evidence text available
Sodium arsenite decreases the amount of USP39.
1 |
Sodium arsenite decreases the amount of USP39. 1 / 1
1 |

No evidence text available
MiR-133a affects USP39
| 2
MiR-133a decreases the amount of USP39.
| 1
MiR-133a decreases the amount of USP39. 1 / 1
| 1

reach
"These data strongly suggest that miR-133a negatively regulates USP39 expression through the translational repression pathway in PC.In this study, our findings provide strong support for a role of elev[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
MiR-133a activates USP39.
| 1
MiR-133a activates USP39. 1 / 1
| 1

reach
"It has been reported that miR-133a inhibits cell progression by targeting USP39 in pancreatic cancer."
Methyl methanesulfonate increases the amount of USP39. 2 / 2
2 |

No evidence text available

No evidence text available
Clr3 affects USP39
| 2
| 2

reach
"These results are consistent with our pull-down assays showing the interaction between Sad1 and Clr3 but no interaction between Sad1 and Sir2 (Figs."

reach
"We then used Microscale thermophoresis (MST) assays to quantitatively characterize the interaction between Sad1 and Clr3."
Citric acid affects USP39
| 2
| 2

reach
"Consistently, citrate supplementation restored mitochondrial respiration and cell growth in USP39-depleted cells."

reach
"USP39 knockdown cells were supplied with citrate and their growth was monitored for the subsequent 72 h. Indeed, citrate supplementation partly restored the growth of USP39-silenced cells (Fig. 4I)."
2 |
Beta-lapachone increases the amount of USP39.
1 |
Beta-lapachone increases the amount of USP39. 1 / 1
1 |

No evidence text available
Beta-lapachone decreases the amount of USP39.
1 |
Beta-lapachone decreases the amount of USP39. 1 / 1
1 |

No evidence text available
All-trans-retinoic acid decreases the amount of USP39. 2 / 2
2 |

No evidence text available

No evidence text available
ZRANB2 affects USP39
1 | 1
1 | 1

No evidence text available

reach
"For example, the interaction between ZRANB2 and USP39, annotated by IntAct and BioGRID, is not correct because the cited article shows instead the interaction between ZRANB1 and USP39."
ZC3H18 affects USP39
2 |
2 |

No evidence text available

No evidence text available
VANGL2 affects USP39
| 2
| 2

sparser
"Usp39 genetically interacts with Vangl2 in axial elongation."

sparser
"Taken together, these findings demonstrate that Usp39 genetically interacts with Vangl2 in terms of axial elongation, supporting the notion that USP39 contributes to modulation of non-canonical Wnt signaling."
USP39 affects splicing efficiency HMGA2
| 2
USP39 activates splicing efficiency HMGA2. 2 / 2
| 2

eidos
"Surprisingly , our work here demonstrated that USP39 improved splicing efficiency of HMGA2 rather than exon skipping ."

eidos
"Consistent with this , loss of USP39 led to decreased splicing efficiency of HMGA2 at both the 5 ' and 3 ' splice sites ( Fig. 7C ) ."

reach
"Cai et al. [52] reported that USP39 promotes PC cell apoptosis by regulating the AKT signaling pathway."

reach
"Xu et al. reported that the knockdown of USP39 increased the levels of apoptosis-related proteins, such as caspase-3, caspase-8, caspase-9, and PARP, in RCCs, and inhibited the activation of ERK and AKT signaling pathways, resulting in an increase in the apoptosis rate of cancer cells [55]."
| 2

reach
"The Sad1-H2A-H2B complex mediates tethering telomeres and the mating-type locus to the NE."

reach
"The Sad1 also mediates telomere attachment to the NE in meiosis through the meiosis-specific Bqt1/Bqt2 complex ."
USP39 affects miR-133a
| 2
USP39 inhibits miR-133a. 2 / 2
| 2

reach
"USP39 is a direct target of miR-133a and partially reversed function of miR-133a."

reach
"Therefore, depletion of USP39 reversed the partial function of miR-133a."
| 1 1
| 1 1

eidos
"Altogether , our data shows that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered as potential target for treating patients with glioma ."

reach
"The similar mechanism of USP39 was also found in human glioma in which USP39 could induce ADAM9 mRNA maturation but not protein to promote glioma progression [53]."
USP39 affects invasion potential ovarian cancer cells
| 2
USP39 activates invasion potential ovarian cancer cells. 2 / 2
| 2

eidos
"D Matrigel invasion data showing that overexpression of USP39 significantly enhanced invasion capacity , whereas knockdown of USP39 ( sh-1 and sh-2 ) decreased the invasion potential of ovarian cancer cells ( n = 3 biologically independent samples ) ."

eidos
"In addition , a transwell invasion assay revealed that forced expression of USP39 significantly enhanced the invasion capacity whereas knockdown of USP39 decreased the invasion potential of ovarian cancer cells ( Fig. 2D ) ."
USP39 affects invasion ovarian cancer cells
| 2
USP39 activates invasion ovarian cancer cells. 2 / 2
| 2

eidos
"USP39 increases proliferation / invasion of ovarian cancer cells and promotes growth of xenograft tumors in mice We next explored whether USP39 was functionally relevant for ovarian progression ."

eidos
"Subsequent functional experiments revealed that USP39 promoted the proliferation and invasion of ovarian cancer cells in vitro ( Fig. 2 ) and tumor growth in vivo ( Fig. 3 ) ."

reach
"In this study, we revealed that the conserved SUN-domain protein Sad1 together with free histone H2A-H2B serves as a previously unrecognized regulatory module to mediate heterochromatin organization near the nuclear periphery (Fig. 7c)."

reach
"These unique properties of Sad1 collectively provide mechanistic insights into Sad1-mediated heterochromatin organization."
USP39 affects growth
| 1 1
USP39 inhibits growth. 1 / 1
| 1

trips
"Knocking down USP39 Inhibits the Growth and Metastasis of Non-Small-Cell Lung Cancer Cells through Activating the p53 Pathway."
USP39 inhibits growth. 1 / 1
| 1

sparser
"Moreover, knockdown of USP39 inhibited ovarian tumor growth in a xenograft model."

reach
"Histone lactylation and USP39 accelerate glycolysis by activating the PI3K/AKT/HIF-1alpha signaling pathway in EC."

reach
"Collectively, these results indicate that histone lactylation and USP39 promote PI3K/AKT- and HIF-1α-mediated glycolysis in EC cells."
USP39 affects clr3
| 2
| 2

reach
"These results are consistent with our pull-down assays showing the interaction between Sad1 and Clr3 but no interaction between Sad1 and Sir2 (Figs."

reach
"We then used Microscale thermophoresis (MST) assays to quantitatively characterize the interaction between Sad1 and Clr3."
USP39 affects carboplatin
| 2
| 2

reach
"Another member of the USP family, USP39, was reported to promote OC malignant phenotypes and carboplatin chemoresistance."

reach
"USP39 promotes ovarian cancer malignant phenotypes and carboplatin chemoresistance."
USP39 affects autophagy
| 2
| 2

reach
"USP39 interacts with SIRT7 to promote cervical squamous cell carcinoma by modulating autophagy and oxidative stress via FOXM1."

reach
"In addition, SIRT7 deacetylates USP39 to promote its protein stability and enhance autophagy, while inhibiting ROS production in CSCC cells [33]."
USP39 affects ZRANB2
1 | 1
1 | 1

No evidence text available

reach
"For example, the interaction between ZRANB2 and USP39, annotated by IntAct and BioGRID, is not correct because the cited article shows instead the interaction between ZRANB1 and USP39."
USP39 affects ZC3H18
2 |
2 |

No evidence text available

No evidence text available
USP39 affects XRCC1
| 2
USP39 inhibits XRCC1. 2 / 2
| 2

reach
"In addition, USP39 knockdown was found to inhibit RCC progression through blocking Akt/ERK pathways [22]."

reach
"USP39 downregulation could inhibit RCC cell proliferation and progression, suggesting that USP39 may prove to be a potential target for inhibiting RCC."
USP39 affects VANGL2
| 2
| 2

sparser
"Usp39 genetically interacts with Vangl2 in axial elongation."

sparser
"Taken together, these findings demonstrate that Usp39 genetically interacts with Vangl2 in terms of axial elongation, supporting the notion that USP39 contributes to modulation of non-canonical Wnt signaling."
USP39 affects TRIM25
2 |
2 |

No evidence text available

No evidence text available
USP39 affects TAFAZZIN
| 2
| 2

reach
"USP39 can also promote the development of glioma by inducing the maturation of TAZ mRNA to increase its protein level [14]."

reach
"Finally, loss of USP39 decreased TAZ pre-mRNA splicing efficiency in glioma cells in vitro, which led to reduced levels of TAZ protein."

reach
"USP39 Promotes the Viability and Migration of Head and Neck Squamous Cell Carcinoma Cell by Regulating STAT1."

reach
"In the present study, we demonstrated that USP39 knockdown inhibited the viability and migration of head and neck squamous cell carcinoma cells."
USP39 affects SRPK2
2 |
2 |

No evidence text available

No evidence text available
USP39 affects SF3B1
2 |
2 |

No evidence text available

No evidence text available
USP39 affects SF3A1
2 |
2 |

No evidence text available

No evidence text available
USP39 affects SAG1
| 2
| 2

reach
"The gametes of different mating types allogenically recognize each other through the interaction of SAD1 and SAG1 and initiate the gamete activation processes, making their apical tips accessible by i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The interaction is strong and may indeed be irreversible, since the Sag1-Sad1 complex is proteolytically shed into the medium [23] ."
USP39 affects RFP
| 2
USP39 binds RFP. 2 / 2
| 2

sparser
"Consequently, we found that red fluorescent protein (RFP) fluorescence was undetectable in cell extracts from either EGFP-GRHL3 or RFP-USP39 transfectants but such fluorescence was obvious in extracts from both reporter constructs that were transfectants (Fig. S xref )."

sparser
"Thus, the VIP assay demonstrated that nanobody beads that bind to EGFP–GRHL3 were able to interact with RFPUSP39 products (Fig. S xref )."
USP39 affects PRPF31
2 |
2 |

No evidence text available

No evidence text available
USP39 affects PRKN
2 |
2 |

No evidence text available

No evidence text available
USP39 affects PI3K/AKT/HIF-1alpha
| 2
USP39 activates PI3K/AKT/HIF-1alpha. 2 / 2
| 2

reach
"Moreover, USP39 activated PI3K/AKT/HIF-1alpha signaling pathway via interacting with and stabilizing PGK1 to stimulate glycolysis."

reach
"Histone lactylation and USP39 accelerate glycolysis by activating the PI3K/AKT/HIF-1alpha signaling pathway in EC."
USP39 affects Melanoma
| 1
| 1

reach
"Similarly, USP39 promotes malignant melanoma progression by regulating ERK signaling [56]."
USP39 affects MRPL35
| 2
USP39 increases the amount of MRPL35. 2 / 2
| 2

reach
"Then, we found that only the knockdown of USP39 reduced MRPL35 expression in H1299 cells compared with other USP enzyme families (Figure 3B)."

reach
"However, MRPL35 protein expression was reduced by USP39 silencing but increased by USP39 overexpression in H1299 and A549 cells (Figure 3E)."
USP39 affects LINC00623
| 2
LINC00623 binds USP39. 2 / 2
| 2

reach
"As a medium for NAT10 to interact with the deubiquitinase USP39, LINC00623 can bind to NAT10 and recruit USP39, thereby improving NAT10 stability by blocking its ubiquitination and degradation."

reach
"In pancreatic cancer, LINC00623 binds to NAT10 and recruits USP39 to block ubiquitin-dependent mRNA degradation, thereby preserving oncogenic mRNA's stability and accelerating a malignant tumor's grow[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects KAT8
2 |
2 |

No evidence text available

No evidence text available
USP39 affects IL6
| 2
USP39 increases the amount of IL6.
| 1
USP39 increases the amount of IL6. 1 / 1
| 1

reach
"The results showed that E overexpression upregulated the mRNA levels of IL-1B, IL-6, TNF-α, and IFN-γ as expected ( Fig. 5 A), while wild type (WT) of USP39 but not △AR and △iUSP mutants further enhan[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 decreases the amount of IL6.
| 1
USP39 decreases the amount of IL6. 1 / 1
| 1

reach
"Correspondingly, knockdown of endogenous USP39 reduced the protein level of E, thereby attenuating E-induced upregulation of the mRNA levels of IL-1B, IL-6, TNF-α, and IFN-γ ( Fig. 5 C and D)."
USP39 affects HLA-B
| 2
USP39 activates HLA-B. 2 / 2
| 2

reach
"USP39 extensively modulates alternative splicing through potential interactions with RBPs."

reach
"USP39 promotes hepatocellular carcinogenesis through regulating alternative splicing in cooperation with SRSF6/HNRNPC."
USP39 affects H3C12
2 |
2 |

No evidence text available

No evidence text available
| 1

reach
"Next, to verify that genomic instability is directly caused by USP39 knockdown, we generated an siRNA-resistant USP39 construct ( USP39) and introduced this construct into cells with ablated endogenous USP39."
| 1

reach
"USP39 ablation induced severe genomic instability similar to LIG4 knockdown, which is a key regulator of NHEJ (Figure 2B and Supplementary Figure S4A)."
USP39 affects EZH2
2 |
2 |

No evidence text available

No evidence text available
USP39 affects DNAAF5
2 |
2 |

No evidence text available

No evidence text available
USP39 affects DNA repair
| 2
| 2

reach
"To determine whether USP39-mediated DNA repair processes are linked to spliceosome activity, we conducted a DNA repair assay using cells depleted of SART1, SART3 or snRNP27, which are critical factors for tri-snRNP complex assembly."

reach
"To further test whether the RG repeats in N46 are critical for regulating USP39-mediated DNA repair and cell survival, we generated RG repeat point mutants with mutations of all RG residues to alanine (hereafter referred to as RG/AA)."

reach
"To ascertain whether USP39 modulates DSB repair, we knocked down USP39 with individual or pooled siRNAs targeting three different USP39 mRNA regions."

reach
"The ATM inhibitor, KU55933, failed to prevent USP39 enrichment in laser-induced DSB-containing stripes (Figure 1E and Supplementary Figure S3A and B)."
USP39 affects DGKG
2 |
2 |

No evidence text available

No evidence text available
USP39 affects DAP
| 2
USP39 binds DAP. 2 / 2
| 2

sparser
"Direct Binding of Dap20‐Linked diUb to USP39 In Vitro."

sparser
"In particular, USP39 was directly and strongly interacted with Dap20‐linked diUb, suggesting a potential role for USP39 in its decoding."

reach
"Overall, the results suggest that USP39 facilitates cell proliferation and decreases cell apoptosis rate in cervical squamous cell carcinoma."

reach
"USP39 interacts with SIRT7 to promote cervical squamous cell carcinoma by modulating autophagy and oxidative stress via FOXM1."
USP39 affects CTLA4
| 1 1
USP39 increases the amount of CTLA4. 2 / 2
| 1 1

sparser
"These results suggest that lactate induces Foxp3 expression and then promotes USP39-dependent CTLA-4 expression in Treg cells."

reach
"This enhanced Treg cell function is partially mediated by lactate-dependent ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, to augment cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in a FOXP3-dependent manner and, thus, to prevent cytotoxic T cell function [128]."
| PMC
USP39 affects CFP
| 2
| 2

sparser
"For colocalization of USP39 or USP14, and RNF5 with E, Hela cells were transfected with E-YFP, USP39-CFP and RNF5-Flag or USP14-Flag and RNF5-CFP, or USP14-Flag and USP39-CFP for 48 h as indicated."

sparser
"Hela cells seeded in 6-well glass-bottom plates were transfected with E-YFP (1 μg) and CFP-USP39 (1 μg), then were treated with 10 μM MG132 to avoid the degradation for 12 h prior to fixing, following[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects CDK1
| 2
USP39 inhibits CDK1.
| 1
USP39 inhibits CDK1. 1 / 1
| 1

reach
"However, treated with PFT-alpha reduced the up-regulation of p21 and BAX induced by USP39 knockdown, but had no effect on the down-regulation of cell cycle related proteins (CDK1 and CyclinB1 and CDK2 and CyclinA2) induced by USP39 knockdown."
USP39 increases the amount of CDK1.
| 1
USP39 increases the amount of CDK1. 1 / 1
| 1

reach
"Besides, both the phosphorylated and basal levels of CDK1 were reduced by USP39 knockdown."
USP39 affects BRD4
2 |
2 |

No evidence text available

No evidence text available
USP39 affects BAX
| 2
USP39 inhibits BAX. 2 / 2
| 2

reach
"However, treated with PFT-alpha reduced the up-regulation of p21 and BAX induced by USP39 knockdown, but had no effect on the down-regulation of cell cycle related proteins (CDK1 and CyclinB1 and CDK2 and CyclinA2) induced by USP39 knockdown."

reach
"Meanwhile, we found that USP39 knockdown also activates the p53 pathway, upregulation of p53, p-p53 (S15), p21 and BAX in HCC827 cells."

reach
"USP39 has been less studied in lung cancer, but there are studies showing that USP39 was upregulated in lung adenocarcinoma cells and promoted the growth of lung adenocarcinoma cells [12]."

reach
"USP39 silencing leads to growth and migration inhibition in lung adenocarcinoma."
USP39 affects 3a
1 1 |
1 1 |

No evidence text available

No evidence text available
TRIM25 affects USP39
2 |
2 |

No evidence text available

No evidence text available
SRPK2 affects USP39
2 |
2 |

No evidence text available

No evidence text available
SF3B1 affects USP39
2 |
2 |

No evidence text available

No evidence text available
SF3A1 affects USP39
2 |
2 |

No evidence text available

No evidence text available
SAG1 affects USP39
| 2
| 2

reach
"The gametes of different mating types allogenically recognize each other through the interaction of SAD1 and SAG1 and initiate the gamete activation processes, making their apical tips accessible by i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The interaction is strong and may indeed be irreversible, since the Sag1-Sad1 complex is proteolytically shed into the medium [23] ."
RFP affects USP39
| 2
USP39 binds RFP. 2 / 2
| 2

sparser
"Consequently, we found that red fluorescent protein (RFP) fluorescence was undetectable in cell extracts from either EGFP-GRHL3 or RFP-USP39 transfectants but such fluorescence was obvious in extracts from both reporter constructs that were transfectants (Fig. S xref )."

sparser
"Thus, the VIP assay demonstrated that nanobody beads that bind to EGFP–GRHL3 were able to interact with RFPUSP39 products (Fig. S xref )."
PRPF31 affects USP39
2 |
2 |

No evidence text available

No evidence text available
PRKN affects USP39
2 |
2 |

No evidence text available

No evidence text available
Mice affects USP39
| 2
Mice activates USP39. 2 / 2
| 2

reach
"To establish the causal relationship between USP39 upregulation and hepatocarcinogenesis, hepatocyte-specific Usp39 overexpression mice (Usp39 ) were generated by crossing Rosa26-stopflox/flox-Usp39 mice with Albumin-Cre mice."

reach
"Crossing Usp39 f/f mice to IgG1-Cre mice in future will enable precise dissection of the role of Usp39 in germinal center responses."
LINC00623 affects USP39
| 2
LINC00623 binds USP39. 2 / 2
| 2

reach
"As a medium for NAT10 to interact with the deubiquitinase USP39, LINC00623 can bind to NAT10 and recruit USP39, thereby improving NAT10 stability by blocking its ubiquitination and degradation."

reach
"In pancreatic cancer, LINC00623 binds to NAT10 and recruits USP39 to block ubiquitin-dependent mRNA degradation, thereby preserving oncogenic mRNA's stability and accelerating a malignant tumor's grow[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
HDA3 affects USP39
| 2
HDA3 phosphorylates USP39. 2 / 2
| 2

reach
"Thus, we presume that Plo1-dependent phosphorylation of Sad1 or another target during prometaphase alters its binding interactions at the SPB to drive ring formation."

reach
"However, as we have yet to detect direct Plo1 phosphorylation of Sad1 and because Plo1 itself does not form a ring, other intermediates may be involved."
H3C12 affects USP39
2 |
2 |

No evidence text available

No evidence text available
Gentamicins affects USP39
2 |
Gentamicins increases the amount of USP39. 2 / 2
2 |

No evidence text available

No evidence text available
EZH2 affects USP39
2 |
2 |

No evidence text available

No evidence text available
EGFR affects USP39
| 2
EGFR activates USP39. 2 / 2
| 2

reach
"To verify whether the regulatory effect of USP39 was EGFR specific, ectopic expression of USP39 were performed in PC-3 and DU145 cells, which showed that overexpressed USP39 upregulated EGFR mRNA and protein levels, indicating that EGFR is a downstream target of USP39."

reach
"EGFR is a downstream target of USP39."
E2F4 affects USP39
| 2
E2F4 activates mutated USP39. 2 / 2
| 2

reach
"Consequently, e2f4 upregulation in usp39 mutants may contribute to increased proliferation of terminally differentiated pituitary cells leading to lineage expansion as seen in our BrdU studies (XREF_SUPPLEMENTARY)."

reach
"In addition, we performed quantitative RT-PCR analysis on the rb1 mRNA injected usp39 embryos and observed a 30% reduction of e2f4 expression compared to control uninjected usp39 mutants (XREF_SUPPLEMENTARY), indicating that e2f4 upregulation in usp39 mutant is secondary to Rb1 loss of function."
DNAAF5 affects USP39
2 |
2 |

No evidence text available

No evidence text available
DGKG affects USP39
2 |
2 |

No evidence text available

No evidence text available
DAP affects USP39
| 2
USP39 binds DAP. 2 / 2
| 2

sparser
"Direct Binding of Dap20‐Linked diUb to USP39 In Vitro."

sparser
"In particular, USP39 was directly and strongly interacted with Dap20‐linked diUb, suggesting a potential role for USP39 in its decoding."
CFP affects USP39
| 2
| 2

sparser
"For colocalization of USP39 or USP14, and RNF5 with E, Hela cells were transfected with E-YFP, USP39-CFP and RNF5-Flag or USP14-Flag and RNF5-CFP, or USP14-Flag and USP39-CFP for 48 h as indicated."

sparser
"Hela cells seeded in 6-well glass-bottom plates were transfected with E-YFP (1 μg) and CFP-USP39 (1 μg), then were treated with 10 μM MG132 to avoid the degradation for 12 h prior to fixing, following[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
BRD4 affects USP39
2 |
2 |

No evidence text available

No evidence text available
Acrylamide affects USP39
2 |
Acrylamide increases the amount of USP39. 2 / 2
2 |

No evidence text available

No evidence text available
ADAM9 affects USP39
| 2
| 2

sparser
"Furthermore, to determine whether USP39 could interact with ADAM9 and regulate the ubiquitination of ADAM9, we co‐transfected Myc‐tagged USP39, Flag‐tagged ADAM9 with or without HA tagged Ub plasmids into HEK293T cells; co‐immunoprecipitation experiments revealed that USP39 failed to interact with ADAM9 at the protein level (Fig.  xref ) and overexpressing USP39 had no effect on the polyubiquitination of ADAM9 (Fig. S9B)."

sparser
"Interestingly, Xiao et al. found that USP39 also directly binds to ADAM9 mRNA and promotes its pre-mRNA maturation, thereby altering the expression and activity of integrin β1 and promoting migration and invasion of human glioma cells ( xref )."
3a affects USP39
1 1 |
1 1 |

No evidence text available

No evidence text available
2 |

No evidence text available

No evidence text available
Type SIRT7 affects USP39
| 1
Type SIRT7 leads to the deacetylation of USP39. 1 / 1
| 1

reach
"Further analysis revealed that USP39 acetylation was inhibited by wild type SIRT7, and the mutant SIRT7 without USP39 acetylation activity (SIRT7 H187Y) was demonstrated to suppress USP39 deacetylation (Fig. 3E)."
1 |
Trovafloxacin decreases the amount of USP39. 1 / 1
1 |

No evidence text available
Trimellitic anhydride increases the amount of USP39. 1 / 1
1 |

No evidence text available
Sorafenib affects USP39
1 |
Sorafenib decreases the amount of USP39. 1 / 1
1 |

No evidence text available
1 |
Sodium arsenate increases the amount of USP39. 1 / 1
1 |

No evidence text available
| 1

sparser
"Therefore, the inhibition of USP39 by shRNA might be a potential therapeutic method in MTC."
Rotenone affects USP39
1 |
Rotenone increases the amount of USP39. 1 / 1
1 |

No evidence text available
Rev affects USP39
1 |
1 |

No evidence text available
Resveratrol affects USP39
1 |
Resveratrol increases the amount of USP39. 1 / 1
1 |

No evidence text available
Ozone affects USP39
1 |
Ozone increases the amount of USP39. 1 / 1
1 |

No evidence text available
Oncogene protein c-MYC ovarian cancer cells affects USP39
| 1
Oncogene protein c-MYC ovarian cancer cells activates USP39. 1 / 1
| 1

eidos
"Importantly , USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells ."
Nimesulide affects USP39
1 |
Nimesulide increases the amount of USP39. 1 / 1
1 |

No evidence text available
MiR-370-3p affects USP39
| 1
MiR-370-3p inhibits USP39. 1 / 1
| 1

reach
"According to dual-luciferase reporter assay and RNA pull-down assay, miR-370-3p was identified to be targeted and sponged by circCLSPN, and further targeted and negatively regulated USP39."
1 |
Methamphetamine increases the amount of USP39. 1 / 1
1 |

No evidence text available
Mercury(0) affects USP39
1 |
Mercury(0) increases the amount of USP39. 1 / 1
1 |

No evidence text available
Ivermectin affects USP39
1 |
Ivermectin decreases the amount of USP39. 1 / 1
1 |

No evidence text available
1 |
Hydrogen peroxide increases the amount of USP39. 1 / 1
1 |

No evidence text available
1 |
Hsa-miR-193b-3p decreases the amount of USP39. 1 / 1
1 |

No evidence text available
Flutamide affects USP39
1 |
Flutamide increases the amount of USP39. 1 / 1
1 |

No evidence text available
| 1
| 1

reach
"One particularly tempting idea is that centromere-dependent Polo localization at the SPB initiates Sad1 reorganization and NEBD."
1 |
Deoxynivalenol dephosphorylates USP39. 1 / 1
1 |

No evidence text available
Bqt2 affects USP39
| 1
| 1

reach
"Taken together, these results showed that Bqt1 directly binds to Bqt2 and to Sad1 and that Bqt2 binds to Sad1 through interaction with Bqt1."
Astaxanthin affects USP39
| 1
| 1

sparser
"Astaxanthin-induced USP39 inhibition promoted β-catenin ubiquitination and degradation, thereby blocking Wnt/β-catenin pathway activation."
1 |
Arsenic disulfide decreases the amount of USP39. 1 / 1
1 |

No evidence text available
YP_009227196 affects USP39
1 |
YP_009227196 binds USP39. 1 / 1
1 |

No evidence text available
WWTR1 affects USP39
1 |
1 |

No evidence text available
WWOX affects USP39
1 |
1 |

No evidence text available
1 |
1 |

No evidence text available
VHL affects USP39
1 |
1 |

No evidence text available
Ualcan databases affects USP39
| 1
Ualcan databases activates USP39. 1 / 1
| 1

eidos
"It was consistent with the observation in Ualcan databases , by which USP39 expression was significantly upregulated in advanced stages and grades of HCC patients ( Supplementary Figures 3A , B ) ."
USP4 affects USP39
| 1
USP39 binds USP4 and UBL domain. 1 / 1
| 1

reach
"USP39 binds with USP4 via its UBL domain and correspondingly enhances the stability of USP4 in T cells [XREF_BIBR, XREF_BIBR], implying that USP39 might be deubiquitylating USP4."
USP39 affects β-amyrin
| 1
USP39 activates β-amyrin. 1 / 1
| 1

reach
"Co-expression of tHMGR and SAD1 in about 460 N. benthamiana plants and cultivation for 5 days allowed successful isolation of 800 mg of β-amyrin with >98% purity."
| 1
| 1

reach
"A similar molecular signature was observed in PAAD, and our experimental findings demonstrated that elevated USP39 expression significantly enhanced cell proliferation and wound healing capacity in PAAD."
USP39 affects volume
| 1
USP39 activates volume. 1 / 1
| 1

eidos
"USP39 depletion led to reduced tumor mass and volume ( Fig. 3B ) ."
USP39 affects stability p53 protein
| 1
USP39 inhibits stability p53 protein. 1 / 1
| 1

eidos
"Furthermore , USP39 knockdown increased the stability of the p53 protein by prolonging its half-life ."
USP39 affects splicing
| 1
USP39 activates splicing. 1 / 1
| 1

eidos
"RNA-sequencing analysis revealed that USP39 depletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions ."
USP39 affects splicing exon-exon minigene transcripts
| 1
USP39 activates splicing exon-exon minigene transcripts. 1 / 1
| 1

eidos
"USP39 depletion markedly reduced the splicing of the three exon-exon minigene transcripts and increased splicing of the exon-intron minigene transcript ( Fig. 7F ) ."
USP39 affects sad2 mutants
| 1
Mutated USP39 activates sad2 mutants. 1 / 1
| 1

reach
"Comparison of root extracts of the wild type, sad1 mutants #109 and #610 with those of two characterised sad2 mutants #791 and #1027 ( Papadopoulou et al., 1999; Qi et al., 2006 ) using a different TL[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects rev
1 |
1 |

No evidence text available
USP39 affects proteolysis
| 1
| 1

reach
"Taken together, these results suggest that USP39 knockdown promotes Cyclin B1 protein degradation in a proteasome-dependent manner."

reach
"Deletion of the USP39 gene could cause the failure of primitive streak formation and embryonic lethality in mice by biological analysis."

reach
"Knockdown of USP39 inhibits malignant transformation of PCa through interrupting the transcription elongation, maturation and stability of EGFR mRNA."
| 1
| 1

reach
"SIRT7/USP39/FOXM1 is highly expressed in CSCC, but whether the pathogenesis in cervical squamous cell carcinoma patients is inhibited by acetylation of USP39 at the k428 site still needs further study."
USP39 affects overall survival mice
| 1
USP39 inhibits overall survival mice. 1 / 1
| 1

eidos
"USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice ."
USP39 affects non-homologous end-joining repair
| 1
USP39 activates non-homologous end-joining repair. 1 / 1
| 1

eidos
"USP39 promotes non-homologous end-joining repair by poly ( ADP-ribose ) - induced liquid demixing ."
USP39 affects metastasis lung cancer cells
| 1
USP39 activates metastasis lung cancer cells. 1 / 1
| 1

eidos
"Together , these data demonstrate that USP39 knockdown inhibits the metastasis of lung cancer cells in vivo and in vitro ."
| 1

reach
"In yeast, the ABH1 homolog CBP80 and the SAD1 homolog Lsm5 are active components of the spliceosome and mediate various steps of RNA metabolism [47], but these two proteins do not seem to interact dir[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"These findings suggest that USP39 contributes to mesendoderm migration via its deubiquitination activity."
USP39 affects mTORC2
| 1
USP39 activates mTORC2. 1 / 1
| 1

reach
"Zhao et al. further indicated that USP39 promoted the proliferation of ESCC cells by enhancing the splicing and maturation of Rictor mRNA, a component of the mTOR complex, and regulating the mTORC2 signaling pathway [50]."
| 1

reach
"For example, USP39 has been reported to be important for the activation of antiviral immune response ( Peng et al., 2020b ), whereas we uncovered a contrasting role for USP39 in promoting SARS-CoV-2 r[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects human glioma cells migration
| 1
USP39 activates human glioma cells migration. 1 / 1
| 1

eidos
"Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation ."
USP39 affects glioma25
| 1
USP39 activates glioma25. 1 / 1
| 1

eidos
"Previously , USP39 depletion was found to cause a significant reduction in pre-mRNA splicing efficiency in colon cancer and glioma25 ,30 ."
| 1

reach
"This enhanced Treg cell function is partially mediated by lactate-dependent ubiquitin-specific peptidase 39 (USP39), a component of the RNA splicing machinery, to augment cytotoxic T-lymphocyte antigen 4 (CTLA-4) expression in a FOXP3-dependent manner and, thus, to prevent cytotoxic T cell function [128]."
| PMC
USP39 affects cytokinesis
| 1
| 1

reach
"As a confirmed spliceosome factor, USP39 is critical to maintain the spindle checkpoint and promote successful cytokinesis through the regulation of Aurora B mRNA splicing in mammalian cells."
USP39 affects colony A549 cells
| 1
USP39 activates colony A549 cells. 1 / 1
| 1

eidos
"USP39 knockdown inhibited the proliferation and colony formation of A549 and HCC827 cells and decreased tumorigenic potential in nude mice ."
USP39 affects cisplatin
| 1
| 1

reach
"For instance, USP39 silencing enhanced cisplatin‐induced apoptosis in colon cancer cells by increasing p53 expression [24]."

reach
"Mis18C recruitment by Sad1 is important for CENP-A Cnp1 chromatin establishment and acts in parallel with a CENP-C-mediated Mis18C recruitment pathway to maintain centromeric CENP-A Cnp1 but operates independently of Sad1-mediated centromere clustering."
USP39 affects cell
| 1
USP39 activates cell. 1 / 1
| 1

eidos
"Here , we prove that USP39 promotes HCC cell proliferation and migration by directly deubiquitin beta-catenin , a key molecular of Wnt / beta-catenin signaling pathway whose abnormal expression or activation results in several tumors , following its co-localization with USP39 ."
USP39 affects cell migration A549 HCC827 cells
| 1
USP39 activates cell migration A549 HCC827 cells. 1 / 1
| 1

eidos
"We further observed that USP39 downregulation inhibits the cell proliferation and migration of A549 and HCC827 cells ."

reach
"We found that USP39 could upregulate Cyclin B1 protein stability to promote G2/M cell cycle transition and glioma cell proliferation, as well as tumor growth in vivo."
USP39 affects bqt2
| 1
| 1

reach
"Taken together, these results showed that Bqt1 directly binds to Bqt2 and to Sad1 and that Bqt2 binds to Sad1 through interaction with Bqt1."
USP39 affects antitumor cisplatin colon cancer cells dependent p53
| 1
USP39 inhibits antitumor cisplatin colon cancer cells dependent p53. 1 / 1
| 1

eidos
"USP39 attenuates the antitumor activity of cisplatin on colon cancer cells dependent on p53 ."

reach
"Since both canonical and non-canonical Wnt pathway signaling is necessary for the formation of LM-epidermal cells , and USP39 was able to induce LM-epidermal cells when canonical Wnt signaling alone was activated (Fig. 3g–p), these findings indicate that USP39 can direct epithelial morphogenesis by enhancing the enrichment of actomyosin networks via activation of non-canonical Wnt signaling."
USP39 affects activation p53 pathway
| 1
USP39 inhibits activation p53 pathway. 1 / 1
| 1

eidos
"Most importantly , the depletion of USP39 was found to result in the activation of the p53 pathway and to promote the expression of the p53 targets p21 , CDC2 , cyclinB1 , MMP2 and MMP9 ."
USP39 affects abnormal cell cycle distribution
| 1
USP39 inhibits abnormal cell cycle distribution. 1 / 1
| 1

eidos
"First , we observed that depletion of USP39 contributes to abnormal cell cycle distribution by inducing cell cycle arrest at G2 / M. Moreover , the underlying mechanism of action of USP39 is partly dependent on activation of the p53 pathway , upregulation of p53 and p21 , and downregulation of CDC2 and CyclinB1 [ 29 ] in A549 cells ."
USP39 affects YY1
| 1
USP39 activates YY1. 1 / 1
| 1

reach
"In contrast, the knockdown of endogenous USP39 restricted the viral mRNA, viral titers in culture supernatant and protein levels of both the SARS-CoV-2 Omicron ( Fig. 7 G–I) and Delta strains ( Fig. 7[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects YP_009227196
1 |
YP_009227196 binds USP39. 1 / 1
1 |

No evidence text available
USP39 affects XRCC4
| 1
USP39 activates XRCC4. 1 / 1
| 1

reach
"USP39 directly drives XRCC4/LIG4 dependent NHEJ repair."
USP39 affects Wnt/β-catenin
| 1
USP39 inhibits Wnt/β-catenin. 1 / 1
| 1

reach
"USP39 knockdown induces cell apoptosis via the regulation the Wnt/β-catenin signaling pathway in colorectal cancer [31]."
USP39 affects WWTR1
1 |
1 |

No evidence text available
USP39 affects WWOX
1 |
1 |

No evidence text available
USP39 affects VHL
1 |
1 |

No evidence text available
USP39 affects VEGF
| 1
USP39 increases the amount of VEGF. 1 / 1
| 1

reach
"USP39 knockdown significantly reduced the expression level of VEGF 165, but had no significant effect on overall VEGF-A (Additional file 1: Figure S1)."
USP39 affects USP4
| 1
USP39 binds USP4 and UBL domain. 1 / 1
| 1

reach
"USP39 binds with USP4 via its UBL domain and correspondingly enhances the stability of USP4 in T cells [XREF_BIBR, XREF_BIBR], implying that USP39 might be deubiquitylating USP4."
USP39 affects USP36
| 1
| 1

sparser
"Most USPs are abnormally expressed in HCC, among which USP36 and USP39 are most closely associated with HCC prognosis."
USP39 affects USP12
1 |
1 |

No evidence text available
USP39 affects UNC-84 homology) protein
| 1
USP39 binds UNC-84 homology) protein. 1 / 1
| 1

reach
"The LINC complex functions as a nuclear envelope-spanning physical bridge connecting the nucleus and cytoskeleton and comprises two protein families: KASH (Klarsicht/ANC-1/Syne-1 homology) domain proteins that interact with the cytoskeleton on the outer nuclear envelope and SUN (Sad1/UNC-84 homology) protein complexes that are bound to the nuclear lamina and chromatin at the inner nuclear envelope ."
USP39 affects UBL domain
| 1
USP39 binds USP4 and UBL domain. 1 / 1
| 1

reach
"USP39 binds with USP4 via its UBL domain and correspondingly enhances the stability of USP4 in T cells [XREF_BIBR, XREF_BIBR], implying that USP39 might be deubiquitylating USP4."
USP39 affects UBE2H
1 |
1 |

No evidence text available
USP39 affects TRIM5
1 |
1 |

No evidence text available
USP39 affects TMEM150C
1 |

No evidence text available
USP39 affects TAZ mRNA
| 1
USP39 inhibits TAZ mRNA. 1 / 1
| 1

eidos
"Besides , USP39 inhibits TAZ mRNA expression and promotes tumor growth in glioma [ 84 ] ."
| PMC
USP39 affects TAF5
1 |
1 |

No evidence text available
USP39 affects Syne homology proteins
| 1
Syne homology proteins binds USP39. 1 / 1
| 1

reach
"In analogy to Klarsicht, Anc-1, and Syne homology proteins that accumulate at the ONM by binding to INM Sad1 and Unc-84 proteins (Sosa et al., 2013), we propose that Atg39 accumulates at the ONM by forming a translumenal bridge through direct or indirect interactions with the INM.We next asked whether the lumenal domain (with its transmembrane [TM] anchor) was sufficient to confer NE targeting and NE blebbing by making sequential N-terminal deletions."
| 1
| 1

eidos
"To test whether USP39 modulate spliceosome activity via SF3B1 , we measured phosphorylated SF3B1 in ovarian cancer cells with USP39 overexpression or knockdown ."
USP39 affects SUPT16H
1 |
1 |

No evidence text available
USP39 affects SUMOylation specific protein
| 1
USP39 activates SUMOylation specific protein. 1 / 1
| 1

reach
"Wen et al. [XREF_BIBR] have reported that USP39 is a target of SUMOylation specific protein (SENP) in the proliferation of PCa cells."
USP39 affects STIP1
1 |
1 |

No evidence text available
USP39 affects SRSF7
1 |
1 |

No evidence text available
USP39 affects SRSF5
1 |
1 |

No evidence text available
USP39 affects SRSF3
1 |
1 |

No evidence text available
USP39 affects SRSF11
1 |
1 |

No evidence text available
USP39 affects SRSF10
1 |
1 |

No evidence text available
USP39 affects SRPK3
1 |
1 |

No evidence text available
USP39 affects SRGN
1 |
1 |

No evidence text available
USP39 affects SON
1 |
1 |

No evidence text available
USP39 affects SNRPF
1 |
1 |

No evidence text available
USP39 affects SNRPC
1 |
1 |

No evidence text available
USP39 affects SNRPA
1 |
1 |

No evidence text available
USP39 affects SNRNP70
1 |
1 |

No evidence text available
USP39 affects SLFN11
1 |
1 |

No evidence text available
USP39 affects SLC2A8
1 |
1 |

No evidence text available
USP39 affects SLC2A1
| 1
USP39 increases the amount of SLC2A1. 1 / 1
| 1

reach
"In addition, we demonstrated by western blotting that the expression of the glycolysis-related proteins GLUT-1, HK2, LDHA, MCT-1, and MCT-4 was decreased by 2-DG treatment and was enhanced by USP39 vectors (Fig. 7F)."
USP39 affects SLC16A4
| 1
USP39 increases the amount of SLC16A4. 1 / 1
| 1

reach
"In addition, we demonstrated by western blotting that the expression of the glycolysis-related proteins GLUT-1, HK2, LDHA, MCT-1, and MCT-4 was decreased by 2-DG treatment and was enhanced by USP39 vectors (Fig. 7F)."
USP39 affects SLC16A1
| 1
USP39 increases the amount of SLC16A1. 1 / 1
| 1

reach
"In addition, we demonstrated by western blotting that the expression of the glycolysis-related proteins GLUT-1, HK2, LDHA, MCT-1, and MCT-4 was decreased by 2-DG treatment and was enhanced by USP39 vectors (Fig. 7F)."
USP39 affects SIRT2
| 1
USP39 increases the amount of SIRT2. 1 / 1
| 1

reach
"USP39 promotes retinal pathological angiogenesis in retinopathy of prematurity by stabilizing SIRT2 expression through deubiquitination."
USP39 affects SF3B6
1 |
1 |

No evidence text available
USP39 affects SCARNA22
1 |

No evidence text available
USP39 affects SAFB
1 |
1 |

No evidence text available
USP39 affects SAE1
1 |
1 |

No evidence text available
USP39 affects RPL22L1
1 |
1 |

No evidence text available
USP39 affects RNU6ATAC
1 |

No evidence text available
USP39 affects RNA-binding
| 1
| 1

reach
"Deubiquitinating enzyme USP39 promotes the growth and metastasis of gastric cancer cells by modulating the degradation of RNA-binding protein RBM39."
| 1
| 1

reach
"A study found that lactate enhances USP39-mediated RNA splicing, promoting cytotoxic T lymphocyte-associated antigen-4 expression in a Foxp3-dependent way, which boosts Treg suppressive function in colorectal cancer patients [78]."
USP39 affects RBM42
1 |
1 |

No evidence text available
USP39 affects RAP1
| 1
| 1

reach
"These results provide an initial scheme for connecting telomeres with the SPB: Sad1 binds Bqt1, which recruits Bqt2, forming the complex that binds Rap1, thus gluing the Rap1 bound telomere to Sad1 ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
USP39 affects RAD18
1 |
1 |

No evidence text available
USP39 affects Prpf8
1 |
1 |

No evidence text available
USP39 affects PRDM9
1 |
1 |

No evidence text available
USP39 affects PHB1
1 |
1 |

No evidence text available
| 1
| 1

reach
"Gan et al. demonstrated that USP39 expression was overexpressed in osteosarcoma and that USP39 knockdown arrested osteosarcoma cells in G2/M phase, thereby inhibiting tumor growth and metastasis (104)."
USP39 affects ORF3
1 |
1 |

No evidence text available
USP39 affects OBSL1
1 |
1 |

No evidence text available
USP39 affects NUPR1
1 |
1 |

No evidence text available
USP39 affects NTRK1
1 |
1 |

No evidence text available
USP39 affects NR3C1
1 |
1 |

No evidence text available
USP39 affects NCSTN
1 |
1 |

No evidence text available
USP39 affects NCL
1 |
1 |

No evidence text available
USP39 affects NCAPD3
1 |
1 |

No evidence text available
USP39 affects N
1 |
N binds USP39. 1 / 1
1 |

No evidence text available
USP39 affects Mis18C
| 1
Mis18C binds USP39. 1 / 1
| 1

reach
"Mis18C recruitment by Sad1 is important for CENP-A Cnp1 chromatin establishment and acts in parallel with a CENP-C-mediated Mis18C recruitment pathway to maintain centromeric CENP-A Cnp1 but operates independently of Sad1-mediated centromere clustering."
USP39 affects Mice
| 1
USP39 inhibits Mice. 1 / 1
| 1

reach
"Deletion of the USP39 gene could cause the failure of primitive streak formation and embryonic lethality in mice by biological analysis."
USP39 affects Metastatic Cells Vitro potential contribution USP39 metastatic capacity A549 HCC827 cells performed Matrigel non-coated Transwell migration coated Transwell invasion assays
| 1
USP39 activates Metastatic Cells Vitro potential contribution USP39 metastatic capacity A549 HCC827 cells performed Matrigel non-coated Transwell migration coated Transwell invasion assays. 1 / 1
| 1

eidos
"Knockdown of USP39 Inhibits Metastatic of Lung Cancer Cells In Vivo and In Vitro To test the potential contribution of USP39 to the metastatic capacity of A549 and HCC827 cells , in vitro , we performed Matrigel non-coated Transwell migration and Matrigel coated Transwell invasion assays ."
USP39 affects MYT1
| 1
USP39 increases the amount of MYT1. 1 / 1
| 1

reach
"USP39 knockdown upregulates phosphorylated (p)-CDC2 and downregulates p-CDC25 C and p-MYT1 expression, whereas no significant changes were observed in total CDC2, CDC25 C, or MYT1 expression."
USP39 affects MYCN
1 |
1 |

No evidence text available
USP39 affects MKI67
| 1
USP39 activates MKI67. 1 / 1
| 1

reach
"The restoration of USP39 expression increased the staining intensity of both GLI1 and Ki67 as compared to samples from USP39 knockdown group (Fig. 7D)."
USP39 affects MEN1
1 |
1 |

No evidence text available
USP39 affects MECP2
1 |
1 |

No evidence text available
| 1
| 1

reach
"Complementary pathway activity analysis using the GSCA database demonstrated that USP39 predominantly activated the cell cycle (47% activation vs. 0% inhibition), DNA damage response (34% activation vs. 0% inhibition), and apoptosis (25% activation vs. 3% inhibition) pathways, while inhibiting RAS/MAPK signaling (0% activation vs. 34% inhibition) (Fig. 2B)."
USP39 affects M phase
| 1
| 1

reach
"USP39 inhibition also induced G /M phase arrest and increased poly (ADP-ribose) polymerase cleavage (Asp214) suggesting that USP39 is critical for GC cell proliferation."
USP39 affects Leukemia
| 1
| 1

reach
"For example, USP39 promotes cell cycle, and proliferation, resulting in the development of leukemia [6] ."
USP39 affects LSM7
1 |
1 |

No evidence text available
USP39 affects LSM4
1 |
1 |

No evidence text available
USP39 affects LRRK2
1 |
1 |

No evidence text available
USP39 affects LIG4
| 1
USP39 activates LIG4. 1 / 1
| 1

reach
"USP39 directly drives XRCC4/LIG4 dependent NHEJ repair."
USP39 affects LDHA
| 1
USP39 increases the amount of LDHA. 1 / 1
| 1

reach
"In addition, we demonstrated by western blotting that the expression of the glycolysis-related proteins GLUT-1, HK2, LDHA, MCT-1, and MCT-4 was decreased by 2-DG treatment and was enhanced by USP39 vectors (Fig. 7F)."
USP39 affects KO mice
| 1
USP39 activates KO mice. 1 / 1
| 1

reach
"These results indicate that the loss of Usp39 severely arrests early B cell development at the pre-pro-B stage in the Mb1-Cre KO mice."
USP39 affects IRF1
| 1
USP39 decreases the amount of IRF1. 1 / 1
| 1

reach
"Liu and colleagues revealed that USP39, by reducing the expression of Caspase 8 and IRF1 while increasing the levels of Sp1, could control the cell cycle of APL, T-ALL, and CML cell lines and reduce their rate of apoptosis [28]."
USP39 affects IL1B
| 1
USP39 decreases the amount of IL1B. 1 / 1
| 1

reach
"Correspondingly, knockdown of endogenous USP39 reduced the protein level of E, thereby attenuating E-induced upregulation of the mRNA levels of IL-1B, IL-6, TNF-α, and IFN-γ ( Fig. 5 C and D)."
USP39 affects ID1
1 |
1 |

No evidence text available
USP39 affects Histone_H2B
| 1

reach
"Sad1 could bind the H2A-H2B heterodimer but not the H3-H4 tetramer (Fig. 1a and Supplementary Fig. 1a)."
USP39 affects Half-Life
| 1
| 1

eidos
"We observe that USP39 stabilizes SP1 protein and prolongs its half-life by promoting its deubiquitylation pathway ."
USP39 affects HTRA4
1 |
1 |

No evidence text available
USP39 affects HSPA4
1 |
1 |

No evidence text available
USP39 affects HSF1
| 1
| 1

sparser
"To provide further evidence for the direct binding of Usp39 to Hsf1 , we performed a RIP assay in AML12 cells overexpressing FLAG-Usp39."
USP39 affects HK3
1 |
1 |

No evidence text available
USP39 affects HK2
| 1
USP39 increases the amount of HK2. 1 / 1
| 1

reach
"In addition, we demonstrated by western blotting that the expression of the glycolysis-related proteins GLUT-1, HK2, LDHA, MCT-1, and MCT-4 was decreased by 2-DG treatment and was enhanced by USP39 vectors (Fig. 7F)."
USP39 affects HIF1
| 1
USP39 increases the amount of HIF1. 1 / 1
| 1

reach
"USP39 efficiently induced the phosphorylation of PI3K and AKT and increased HIF-1α expression in EC cells (Fig. 7A, B)."
USP39 affects H3-3B
1 |
1 |

No evidence text available
USP39 affects H2AB.Notably
| 1
USP39 binds H2AB.Notably. 1 / 1
| 1

reach
"Thus, our mutagenesis analyzes supported the importance of hydrophobic and electrostatic interactions in coordinating the interaction between Sad1 and H2AB.Notably, the core histone-binding fragment of Sad1 contains a DEF/Y motif commonly identified in H2A-H2B or H2A.Z-H2B-binding proteins, including Chz1, Anp32e, Swr1, and the suppressor of Ty16 (Spt16) (Fig. 2e), and showed a conserved histone recognition mode (Supplementary Fig. 5)."
USP39 affects GTF3C1
1 |
1 |

No evidence text available
USP39 affects G3BP2
| 1
USP39 increases the amount of G3BP2. 1 / 1
| 1

reach
"Combined with the LC-MS/MS analysis, we transfected a list of DUBs cDNA plasmids into HEK293 cells, and surprisingly found that USP7, USP8, USP39 upregulated G3BP2 expression (Fig. 2G)."
USP39 affects FXR2
1 |
1 |

No evidence text available
USP39 affects FBXO22
1 |
1 |

No evidence text available
USP39 affects FANCD2
1 |
1 |

No evidence text available

reach
"The Deubiquitinase USP39 Promotes Esophageal Squamous Cell Carcinoma Malignancy as a Splicing Factor."
USP39 affects ESR2
1 |
1 |

No evidence text available
USP39 affects EAPP
1 |
1 |

No evidence text available
| 1

sparser
"Although the specific E3 ligases that interact with USP39 are not yet fully understood, research suggests that USP39 may inhibit the activity of certain E3 ligases (such as MDM2, TRIM family members, etc.) to prevent ubiquitination and degradation of MRPL35."
| 1

reach
"Further studies are warranted to investigate the precise mechanism by which the USP39-mediated inhibition of ETS2’s nuclear localization occurs and subsequently leads to the transcriptional suppression of ETS2.USP39 has been traditionally considered an inactive DUB due to the substitution of the conserved cysteine residue at amino acid 234 in its USP domain with aspartate [30,31,32]."
USP39 affects Death
| 1
USP39 inhibits Death. 1 / 1
| 1

reach
"Importantly, cell death analysis indicated that USP39 depletion promoted cancer cell death (Fig. 3E)."
USP39 affects DHX9
1 |
1 |

No evidence text available
USP39 affects DDX24
1 |
1 |

No evidence text available
USP39 affects DDX21
1 |
1 |

No evidence text available
USP39 affects DDRGK1
1 |
1 |

No evidence text available
USP39 affects CyclinB1
| 1
USP39 inhibits CyclinB1. 1 / 1
| 1

reach
"However, treated with PFT-alpha reduced the up-regulation of p21 and BAX induced by USP39 knockdown, but had no effect on the down-regulation of cell cycle related proteins (CDK1 and CyclinB1 and CDK2 and CyclinA2) induced by USP39 knockdown."
| 1

eidos
"Previously , USP39 depletion was found to cause a significant reduction in pre-mRNA splicing efficiency in colon cancer and glioma25 ,30 ."
USP39 affects Chmp3
1 |
1 |

No evidence text available
| 1
USP39 increases the amount of Cell Polarity. 1 / 1
| 1

reach
"Such USP39-dependent functions appear to be partly mediated by upregulating expression of PCP components through its deubiquitinating activity rather than the splicing process."

reach
"USP39 promotes malignant proliferation and angiogenesis of renal cell carcinoma by inhibiting VEGF-A 165b alternative splicing via regulating SRSF1 and SRPK1."
USP39 affects CXXC1
1 |
1 |

No evidence text available
USP39 affects CSNK1E
1 |
1 |

No evidence text available
USP39 affects CPSF6
1 |
1 |

No evidence text available
USP39 affects COPRS
1 |
1 |

No evidence text available
USP39 affects CMTR1
1 |
1 |

No evidence text available
USP39 affects CHD4
1 |
1 |

No evidence text available
USP39 affects CDC5L
1 |
1 |

No evidence text available
USP39 affects CDC2 cyclinB1
| 1
USP39 activates CDC2 cyclinB1. 1 / 1
| 1

eidos
"Additionally , USP39 knockdown led to downregulation of CDC2 , cyclinB1 , MMP2 and MMP9 through activating the p53 pathway ( Figure 6A ) ."
USP39 affects CDC123
1 |
1 |

No evidence text available
USP39 affects CCNA2
| 1
USP39 inhibits CCNA2. 1 / 1
| 1

reach
"However, treated with PFT-alpha reduced the up-regulation of p21 and BAX induced by USP39 knockdown, but had no effect on the down-regulation of cell cycle related proteins (CDK1 and CyclinB1 and CDK2 and CyclinA2) induced by USP39 knockdown."
USP39 affects CASP3
| 1
USP39 inhibits CASP3. 1 / 1
| 1

reach
"USP39 overexpression impedes PARP and Caspase3 activation, diminishing the apoptotic rate in ESCC cells treated with cisplatin [53]."
USP39 affects CAND1
1 |
1 |

No evidence text available
USP39 affects C9orf78
1 |
1 |

No evidence text available
USP39 affects BRD7
1 |
1 |

No evidence text available
USP39 affects BRD2
1 |
1 |

No evidence text available
USP39 affects BCAT2
1 |
1 |

No evidence text available
USP39 affects Apc2
1 |
1 |

No evidence text available
USP39 affects AURKB
1 |
1 |

No evidence text available
USP39 affects ARHGAP36
1 |

No evidence text available
USP39 affects ARHGAP24
1 |

No evidence text available
USP39 affects APP
1 |
1 |

No evidence text available
| 1

reach
"USP39/SMC4 promotes hepatoma cell proliferation and 5-FU resistance."

reach
"Furthermore, Des-acyl avenacin A (DAA) and Des-acyl avenacin B (DAB) are synthesized within the cytoplasm by SAD1, SAD2, and other enzymes (Mylona et al., 2008; Mugford et al., 2013; Owatworakit et al., 2013)."
USP36 affects USP39
| 1
| 1

sparser
"Most USPs are abnormally expressed in HCC, among which USP36 and USP39 are most closely associated with HCC prognosis."
USP12 affects USP39
1 |
1 |

No evidence text available
UNC-84 homology) protein affects USP39
| 1
USP39 binds UNC-84 homology) protein. 1 / 1
| 1

reach
"The LINC complex functions as a nuclear envelope-spanning physical bridge connecting the nucleus and cytoskeleton and comprises two protein families: KASH (Klarsicht/ANC-1/Syne-1 homology) domain proteins that interact with the cytoskeleton on the outer nuclear envelope and SUN (Sad1/UNC-84 homology) protein complexes that are bound to the nuclear lamina and chromatin at the inner nuclear envelope ."
UBL domain affects USP4
| 1
USP39 binds USP4 and UBL domain. 1 / 1
| 1

reach
"USP39 binds with USP4 via its UBL domain and correspondingly enhances the stability of USP4 in T cells [XREF_BIBR, XREF_BIBR], implying that USP39 might be deubiquitylating USP4."
UBE2H affects USP39
1 |
1 |

No evidence text available
TSN affects USP39
| 1
TSN inhibits USP39. 1 / 1
| 1

reach
"Meanwhile, TSN reduced PCa tumor growth by regulating USP39/PLK1."
TRIM5 affects USP39
1 |
1 |

No evidence text available
TMEM150C affects USP39
1 |

No evidence text available
TAF5 affects USP39
1 |
1 |

No evidence text available
Syne homology proteins affects USP39
| 1
Syne homology proteins binds USP39. 1 / 1
| 1

reach
"In analogy to Klarsicht, Anc-1, and Syne homology proteins that accumulate at the ONM by binding to INM Sad1 and Unc-84 proteins (Sosa et al., 2013), we propose that Atg39 accumulates at the ONM by forming a translumenal bridge through direct or indirect interactions with the INM.We next asked whether the lumenal domain (with its transmembrane [TM] anchor) was sufficient to confer NE targeting and NE blebbing by making sequential N-terminal deletions."
SUPT16H affects USP39
1 |
1 |

No evidence text available
STIP1 affects USP39
1 |
1 |

No evidence text available
SRSF7 affects USP39
1 |
1 |

No evidence text available
SRSF5 affects USP39
1 |
1 |

No evidence text available
SRSF3 affects USP39
1 |
1 |

No evidence text available
SRSF11 affects USP39
1 |
1 |

No evidence text available
SRSF10 affects USP39
1 |
1 |

No evidence text available
SRPK3 affects USP39
1 |
1 |

No evidence text available
SRGN affects USP39
1 |
1 |

No evidence text available
SON affects USP39
1 |
1 |

No evidence text available
SNRPF affects USP39
1 |
1 |

No evidence text available
SNRPC affects USP39
1 |
1 |

No evidence text available
SNRPA affects USP39
1 |
1 |

No evidence text available
SNRNP70 affects USP39
1 |
1 |

No evidence text available
SNRNP200 affects USP39
1 |

No evidence text available
SLFN11 affects USP39
1 |
1 |

No evidence text available
SLC2A8 affects USP39
1 |
1 |

No evidence text available
SIRT5 affects USP39
| 1
SIRT5 increases the amount of USP39. 1 / 1
| 1

reach
"Another study revealed that SIRT5 negatively modulates the expression of SAD1/UNC84 domain protein 2 (SUN2), a crucial subunit of the linker of nucleoskeleton and cytoskeleton (LINC) complex [118]."
SF3B6 affects USP39
1 |
1 |

No evidence text available
SCARNA22 affects USP39
1 |

No evidence text available
SAFB affects USP39
1 |
1 |

No evidence text available
SAE1 affects USP39
1 |
1 |

No evidence text available
RPL22L1 affects USP39
1 |
1 |

No evidence text available
RNU6ATAC affects USP39
1 |

No evidence text available
RBM42 affects USP39
1 |
1 |

No evidence text available
RAP1 affects USP39
| 1
| 1

reach
"These results provide an initial scheme for connecting telomeres with the SPB: Sad1 binds Bqt1, which recruits Bqt2, forming the complex that binds Rap1, thus gluing the Rap1 bound telomere to Sad1 ( [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
RAD18 affects USP39
1 |
1 |

No evidence text available
Prpf8 affects USP39
1 |
1 |

No evidence text available
1 |
Plant Extracts increases the amount of USP39. 1 / 1
1 |

No evidence text available
PUX9 affects USP39
| 1
PUX9 bound to VCP inhibits USP39. 1 / 1
| 1

reach
"PUX7, PUX8, PUX9, and PUX13 are autophagy adapters for the clearance of nonfunctional CDC48 proteins , and PUX3, PUX4, and PUX5 associate with CDC48 but negatively regulate the stability of the inner nuclear membrane protein SAD1/UNC-84 DOMAIN PROTEIN 1 (SUN1) ."
PUX13 affects USP39
| 1
PUX13 bound to VCP inhibits USP39. 1 / 1
| 1

reach
"PUX7, PUX8, PUX9, and PUX13 are autophagy adapters for the clearance of nonfunctional CDC48 proteins , and PUX3, PUX4, and PUX5 associate with CDC48 but negatively regulate the stability of the inner nuclear membrane protein SAD1/UNC-84 DOMAIN PROTEIN 1 (SUN1) ."
PRDM9 affects USP39
1 |
1 |

No evidence text available
PHB1 affects USP39
1 |
1 |

No evidence text available
PARP1 affects USP39
| 1
| 1

sparser
"Wang et al. found that USP39 can interact with PARP protein, and by knocking down USP39, the cleavage of amino acid 214 of PARP protein was increased, resulting in the loss of PARP protein function and promoting apoptosis in gastric cancer cells ( xref )."
ORF3 affects USP39
1 |
1 |

No evidence text available
OBSL1 affects USP39
1 |
1 |

No evidence text available
NUPR1 affects USP39
1 |
1 |

No evidence text available
NTRK1 affects USP39
1 |
1 |

No evidence text available
NR3C1 affects USP39
1 |
1 |

No evidence text available
NPC affects USP39
| 1
NPC activates USP39. 1 / 1
| 1

reach
"These results indicated that LINC00520 promoted NPC cell growth via acting as a ceRNA for miR-26b-3p.Partially through sponging miR-26b-3p, and then up-regulating USP39, LINC00520 facilitates NPC cell[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
NCSTN affects USP39
1 |
1 |

No evidence text available
NCL affects USP39
1 |
1 |

No evidence text available
NCAPD3 affects USP39
1 |
1 |

No evidence text available
N affects USP39
1 |
N binds USP39. 1 / 1
1 |

No evidence text available
Mis18C affects USP39
| 1
Mis18C binds USP39. 1 / 1
| 1

reach
"Mis18C recruitment by Sad1 is important for CENP-A Cnp1 chromatin establishment and acts in parallel with a CENP-C-mediated Mis18C recruitment pathway to maintain centromeric CENP-A Cnp1 but operates independently of Sad1-mediated centromere clustering."
MYCN affects USP39
1 |
1 |

No evidence text available
MEN1 affects USP39
1 |
1 |

No evidence text available
MECP2 affects USP39
1 |
1 |

No evidence text available
Long non-coding RNA LINC00623 affects USP39
| 1
Long non-coding RNA LINC00623 inhibits USP39. 1 / 1
| 1

reach
"Long non-coding RNA LINC00623 interacts with NAT10 to block the ubiquitination-dependent degradation of NAT10 by recruiting the deubiquitinase USP39 [62]."
LSM7 affects USP39
1 |
1 |

No evidence text available
LSM4 affects USP39
1 |
1 |

No evidence text available
LRRK2 affects USP39
1 |
1 |

No evidence text available
KANK2 affects USP39
| 1
KANK2 activates USP39. 1 / 1
| 1

reach
"By applying the Tet-On system to replenish KANK2 expression upon doxycycline induction, we found that restoration of KANK2 partially reversed the adverse effects of USP39 knockdown on HCC cell proliferation and cell cycle control (Figs."
JTB affects USP39
| 1
JTB activates USP39. 1 / 1
| 1

reach
"This leads to the hypothesis that PAR chains could induce the assembly of USP39 at the end of liquid demixing in a similar way."
ID1 affects USP39
1 |
1 |

No evidence text available
Histone_H2B affects USP39
| 1

reach
"Sad1 could bind the H2A-H2B heterodimer but not the H3-H4 tetramer (Fig. 1a and Supplementary Fig. 1a)."
HTRA4 affects USP39
1 |
1 |

No evidence text available
HSPA4 affects USP39
1 |
1 |

No evidence text available
HSF1 affects USP39
| 1
| 1

sparser
"To provide further evidence for the direct binding of Usp39 to Hsf1 , we performed a RIP assay in AML12 cells overexpressing FLAG-Usp39."
HK3 affects USP39
1 |
1 |

No evidence text available
H3-3B affects USP39
1 |
1 |

No evidence text available
H2AB.Notably affects USP39
| 1
USP39 binds H2AB.Notably. 1 / 1
| 1

reach
"Thus, our mutagenesis analyzes supported the importance of hydrophobic and electrostatic interactions in coordinating the interaction between Sad1 and H2AB.Notably, the core histone-binding fragment of Sad1 contains a DEF/Y motif commonly identified in H2A-H2B or H2A.Z-H2B-binding proteins, including Chz1, Anp32e, Swr1, and the suppressor of Ty16 (Spt16) (Fig. 2e), and showed a conserved histone recognition mode (Supplementary Fig. 5)."
H2AB-RFP affects USP39
| 1
H2AB-RFP activates USP39. 1 / 1
| 1

reach
"Fluorescence images of mixed H2AB-RFP and Sad1 -GFP proteins showed that H2AB substantially augmented the phase separation of Sad1 -GFP (Fig. 6k–m)."
Glyphosate affects USP39
1 |
Glyphosate increases the amount of USP39. 1 / 1
1 |

No evidence text available
GTF3C1 affects USP39
1 |
1 |

No evidence text available
FXR2 affects USP39
1 |
1 |

No evidence text available
FBXO22 affects USP39
1 |
1 |

No evidence text available
FANCD2 affects USP39
1 |
1 |

No evidence text available
ESR2 affects USP39
1 |
1 |

No evidence text available
EAPP affects USP39
1 |
1 |

No evidence text available
| 1

sparser
"Although the specific E3 ligases that interact with USP39 are not yet fully understood, research suggests that USP39 may inhibit the activity of certain E3 ligases (such as MDM2, TRIM family members, etc.) to prevent ubiquitination and degradation of MRPL35."
DHX9 affects USP39
1 |
1 |

No evidence text available
DDX24 affects USP39
1 |
1 |

No evidence text available
DDX21 affects USP39
1 |
1 |

No evidence text available
DDRGK1 affects USP39
1 |
1 |

No evidence text available
Clr3.To affects USP39
| 1
Clr3.To activates USP39. 1 / 1
| 1

reach
"These data suggest that H2A-H2B could enhance the interaction between Sad1 and HDACs, including Sir2 and Clr3.To further support the role of Sad1 in recruiting HDACs, we used ChIP-qPCR assay to examine how Sad1 affects the enrichment of Sir2 in telomere regions."
Chmp3 affects USP39
1 |
1 |

No evidence text available
Carcinoma, Endometrioid decreases the amount of USP39. 1 / 1
| 1

reach
"Next, EC cell lines were transfected with si-USP39 to downregulate the expression of USP39."
CYP71BL3 affects USP39
| 1
CYP71BL3 increases the amount of USP39. 1 / 1
| 1

reach
"Our current results revealed that COS enhanced the expression of aldose 1-epimerase, NADH, Ndufs6, Ndufal3, chlorophyll a -b binding protein, Sm, Lsm and Sad1 complexes, calcium ion binding protein an[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
CXXC1 affects USP39
1 |
1 |

No evidence text available
CSNK1E affects USP39
1 |
1 |

No evidence text available
CPSF6 affects USP39
1 |
1 |

No evidence text available
COPRS affects USP39
1 |
1 |

No evidence text available
CMTR1 affects USP39
1 |
1 |

No evidence text available
CHD4 affects USP39
1 |
1 |

No evidence text available
CDC5L affects USP39
1 |
1 |

No evidence text available
CDC123 affects USP39
1 |
1 |

No evidence text available
CAND1 affects USP39
1 |
1 |

No evidence text available
C9orf78 affects USP39
1 |
1 |

No evidence text available
BRD7 affects USP39
1 |
1 |

No evidence text available
BRD2 affects USP39
1 |
1 |

No evidence text available
BCAT2 affects USP39
1 |
1 |

No evidence text available
Apc2 affects USP39
1 |
1 |

No evidence text available
1 |
Air Pollutants increases the amount of USP39. 1 / 1
1 |

No evidence text available
AURKB affects USP39
1 |
1 |

No evidence text available
ARHGAP36 affects USP39
1 |

No evidence text available
ARHGAP24 affects USP39
1 |

No evidence text available
AR affects USP39
| 1
AR decreases the amount of USP39. 1 / 1
| 1

reach
"PCa cells, especially the AR-negative PCa cells have upregulated expression levels of USP39 (Huang et al., 2016)."
APP affects USP39
1 |
1 |

No evidence text available
1 |

No evidence text available
17alpha-ethynylestradiol increases the amount of USP39. 1 / 1
1 |

No evidence text available
1,2-dimethylhydrazine increases the amount of USP39. 1 / 1
1 |

No evidence text available
4,4'-sulfonyldiphenol increases the amount of USP39. 1 / 1
1 |

No evidence text available

No evidence text available