| 2011 |
USP13 deubiquitinates Beclin1, and Beclin1 in turn controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. USP13 (with USP10) targets the Beclin1 subunit of Vps34 PI3 kinase complexes; inhibition of USP13 promotes degradation of Vps34 complexes. Because USP10 mediates deubiquitination of p53, Beclin1 regulation of USP13/USP10 activity connects p53 levels to autophagy. |
Small-molecule inhibitor (spautin-1) targeting USP10/USP13, Co-IP, protein stability assays in cells |
Cell |
High |
21962518
|
| 2011 |
USP13 deubiquitinates MITF (microphthalmia-associated transcription factor), stabilizing MITF protein levels. Knockdown of USP13 leads to loss of MITF protein without affecting mRNA, demonstrating post-translational stabilization. USP13 modulates MITF downstream target gene expression and is required for melanoma growth. |
shRNA library screen against DUBs, USP13 knockdown, protein stability assays, in vivo nude mouse xenograft |
Nature communications |
High |
21811243
|
| 2011 |
USP13 regulates Siah2 E3 ubiquitin ligase stability and activity via its ubiquitin-binding domains (UBA and UBP domains) rather than its catalytic isopeptidase activity. USP13 binds ubiquitinated Siah2 and prevents its autodegradation, but this effect is abolished by mutations in ubiquitin-binding sequences, not catalytic site mutations. Consequently, USP13 attenuates Siah2's ability to target its substrates (PHD3, Spry2). |
Overexpression, shRNA knockdown, site-directed mutagenesis of catalytic and ubiquitin-binding domains, protein stability assays |
The Journal of biological chemistry |
High |
21659512
|
| 2011 |
USP13 exhibits weak deubiquitinating activity preferring K63-linked polyubiquitin, operating in a non-activation manner. The ZnF domain of USP13, unlike that of its paralog USP5, cannot bind free ubiquitin and therefore USP13 cannot be activated by free ubiquitin. Substitution of the USP13 ZnF domain with the USP5 ZnF domain confers catalytic activation. The tandem UBA domains preferentially bind K63-linked diubiquitin, explaining the substrate preference. |
Biochemical DUB assays with K48/K63 polyubiquitin substrates, NMR structural analysis of ZnF domain, domain-swap mutagenesis, cell-based CD3δ regulation assay |
PloS one |
High |
22216260
|
| 2013 |
USP13 physically associates with PTEN and deubiquitinates PTEN to stabilize its protein levels. Loss of USP13 in breast cancer cells promotes AKT phosphorylation, proliferation, anchorage-independent growth, and glycolysis through downregulation of PTEN. |
DUB screen (30 DUBs) for PTEN physical association, Co-IP, in vitro deubiquitination assay, USP13 knockdown/overexpression, in vivo xenograft |
Nature cell biology |
High |
24270891
|
| 2014 |
USP13 is a gp78-associated deubiquitinase that removes ubiquitin conjugates from Ubl4A (a component of the Bag6 chaperone complex), preventing gp78-mediated polyubiquitination and irreversible proteolytic inactivation of Bag6. This maintains the functionality of the Bag6 chaperone complex in ERAD, sharpening substrate specificity for the gp78 E3 ligase. |
Co-IP identifying USP13 association with gp78, in vitro ubiquitination/deubiquitination assays, cell-based ERAD substrate degradation assays |
eLife |
High |
24424410
|
| 2016 |
USP13 deubiquitinates and stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination of c-Myc, thereby maintaining glioblastoma stem cell (GSC) self-renewal and tumorigenic potential. Depletion of USP13 promotes c-Myc ubiquitination and degradation. The ubiquitin-insensitive T58A-c-Myc mutant rescues the effects of USP13 disruption or FBXL14 overexpression. |
Co-IP, ubiquitination assays, USP13 knockdown/overexpression, T58A-c-Myc rescue experiments, in vivo tumor growth assays |
The Journal of experimental medicine |
High |
27923907
|
| 2016 |
USP13 specifically deubiquitinates and upregulates ATP citrate lyase (ACLY) and oxoglutarate dehydrogenase (OGDH), two key metabolic enzymes determining mitochondrial respiration, glutaminolysis, and fatty acid synthesis in ovarian cancer cells. |
Co-IP, deubiquitination assays, knockdown/overexpression with metabolic readouts, in vivo ovarian tumor models |
Nature communications |
High |
27892457
|
| 2017 |
USP13 interacts with STING and deconjugates polyubiquitin chains from STING, preventing the recruitment of TBK1 to the STING signaling complex and thereby negatively regulating antiviral responses. USP13 knockout mice are more resistant to lethal HSV-1 infection. |
Co-IP identifying USP13-STING interaction, in vitro deubiquitination assay, USP13 KD/KO cells and knockout mice, IRF3/NF-κB activation assays, viral replication assays |
Nature communications |
High |
28534493
|
| 2017 |
USP13 is phosphorylated by ATM kinase following DNA damage, which facilitates its localization to DNA double-strand breaks (DSBs). USP13 then deubiquitinates RAP80, promoting RAP80 recruitment and proper DNA damage response (DDR) including BRCA1 complex foci formation. |
Co-IP, phosphorylation assays, DSB localization by immunofluorescence, RAP80 ubiquitination assays, USP13 depletion/inhibition sensitivity assays in ovarian cancer cells |
Nature communications |
High |
28569838
|
| 2018 |
USP13 interacts with and stabilizes MCL1 via deubiquitination, regulating MCL1 turnover in lung and ovarian cancer cells. CRISPR/Cas9-mediated USP13 depletion reduces MCL1 protein abundance and increases sensitivity to BH3 mimetic inhibitors. |
Unbiased siRNA screen, Co-IP, deubiquitination assay, CRISPR/Cas9 KO, in vivo xenograft, BH3 mimetic sensitivity assays |
Nature communications |
High |
29335437
|
| 2018 |
USP5 and USP13 are recruited to heat-induced stress granules via their deubiquitylating activities. Depletion of USP13 elevates ubiquitin chain levels in stress granules, accelerates their assembly, and markedly impairs their disassembly after heat stress removal. USP13 regulates stress granule dynamics by deubiquitylating protein-conjugated ubiquitin chains. |
Immunofluorescence recruitment assay, siRNA knockdown, ubiquitin chain level measurements, stress granule assembly/disassembly kinetics |
Journal of cell science |
Medium |
29567855
|
| 2020 |
The E3 ubiquitin ligase NEDD4-1 undergoes K29-linked auto-ubiquitination at K1279, which serves as a scaffold to recruit USP13. The resulting NEDD4-1–USP13 complex deubiquitinates VPS34/PIK3C3 by removing K48-linked poly-ubiquitin chains at K419, stabilizing VPS34 and promoting autophagy initiation. |
Co-IP, deubiquitination assay, ubiquitin linkage-specific analysis, NEDD4-1 and USP13 KO cell lines, autophagosome formation assays |
Cell reports |
High |
32101753
|
| 2020 |
USP13 interacts with cohesin and its ubiquitin-binding domains (UBA1/2) are required for this interaction. The interaction occurs specifically in the soluble nuclear fraction and preferentially during DNA replication. USP13 is paradoxically required for both deubiquitination and ubiquitination of cohesin subunits, and is required for dissociation of cohesin from chromatin as cells transit through mitosis, but is dispensable for sister chromatid cohesion. |
Endogenous dual-affinity purification + mass spectrometry, Co-IP in multiple cell lines, domain mapping (UBA1/2 mutants), CRISPR KO, cell fractionation, mitotic chromosome spreads |
The Journal of biological chemistry |
High |
33334891
|
| 2020 |
USP13 associates with Aurora B kinase and stabilizes Aurora B, especially before mitotic entry. Aurora B-mediated phosphorylation of USP13 at Serine 114 promotes their association. USP13 instigates Aurora B deubiquitination and/or protects it from degradation in a manner that may be partially non-catalytic. Modulation of USP13 levels/activity affects unperturbed cell-cycle progression. |
Co-IP, phosphorylation assays, USP13 gain/loss-of-function, protein stability assays, cell cycle analysis |
Oncogene |
Medium |
32772043
|
| 2020 |
USP13 deubiquitinates and stabilizes Smad4 in lung fibroblast cells. USP13 and Smad4 co-localize in the cytoplasm and co-translocate to the nucleus in response to TGF-β1. USP13 deficiency in mice reduces extracellular matrix (ECM) protein levels, demonstrating a role in ECM expression regulation through Smad4 stabilization. |
Co-IP, pulse-chase protein stability assay, USP13 KO mice, overexpression/knockdown, immunofluorescence co-localization |
Translational research |
Medium |
32434004
|
| 2019 |
USP13 deubiquitinates and stabilizes IL-1R8/Sigirr, an anti-inflammatory receptor. USP13 levels directly correlate with IL-1R8/Sigirr; knockdown increases IL-1R8/Sigirr poly-ubiquitination and degradation, enhancing TLR4 signaling and cytokine release. USP13-deficient mice are highly susceptible to LPS- and Pseudomonas-induced lung injury, and IL-1R8/Sigirr overexpression rescues the inflammatory phenotype. |
Receptor ligation chase model, Co-IP, poly-ubiquitination assay, USP13 KO mice, acute lung injury model, IL-1R8/Sigirr overexpression rescue |
EBioMedicine |
High |
31204278
|
| 2021 |
USP13 binds to TopBP1 and stabilizes it via deubiquitination, facilitating ATR activation in response to replication stress. Depletion of USP13 impedes ATR activation and hypersensitizes cells to replication stress-inducing agents. |
Co-IP, deubiquitination assay, USP13 knockdown, ATR activation assays, replication stress sensitivity assays |
DNA repair |
Medium |
33592542
|
| 2021 |
USP13 interacts with Snail transcription factor and deubiquitinates it, stabilizing Snail protein and promoting EMT and metastasis in gastric cancer. USP13 knockdown promotes Snail degradation blockable by proteasome inhibitor MG132; Snail knockdown blocks USP13-induced migration. |
Co-IP, deubiquitination assay, proteasome inhibitor rescue, knockdown/overexpression, migration/invasion assays |
Pathology, research and practice |
Medium |
34872023
|
| 2021 |
USP13 deubiquitinates and stabilizes Mcl-1 in cervical cancer cells. USP13 depletion reduces Mcl-1 expression, inhibits cell proliferation, and increases sensitivity to BH3 mimetic ABT-263. |
Co-IP, deubiquitination assay, USP13 knockdown, Mcl-1 stability assays, BH3 mimetic sensitivity |
Oncogene |
Medium |
33627786
|
| 2021 |
USP13 deubiquitinates IRAK4 in macrophages. Myeloid-specific USP13 deficiency increases LPS-induced pro-inflammatory responses and worsens septic symptoms in mice, which can be rescued by IRAK4 inhibitor co-administration. |
USP13 myeloid-specific KO mice (USP13MKO), Co-IP/deubiquitination assay, IRAK4 inhibitor rescue, BMDM inflammatory assays, sepsis mouse model |
Microbes and infection |
Medium |
34298177
|
| 2022 |
USP13 binds ZHX2 (Zinc Fingers And Homeoboxes 2) and promotes ZHX2 deubiquitination and protein stability in an enzymatically dependent manner. USP13 depletion leads to ZHX2 downregulation and decreased ccRCC cell proliferation. |
DUB cDNA library binding screen, Co-IP, deubiquitination assay, USP13 depletion, 2D/3D growth assays, in vivo tumor growth |
PNAS |
Medium |
36037364
|
| 2022 |
N6-methyladenosine (m6A) modification by METTL3 (read by IGF2BP2) stabilizes USP13 mRNA. USP13 protein interacts with ATG5 and stabilizes ATG5 via deubiquitination; PAK1 kinase-mediated phosphorylation of ATG5 enhances its interaction with USP13. This USP13-ATG5 axis enhances autophagy and imatinib resistance in GIST cells. |
Co-IP, deubiquitination assay, PAK1 phosphorylation assay, m6A-seq, USP13 inhibitor (spautin-1) + 3-MA treatment in xenograft models |
Cell death and differentiation |
Medium |
36528756
|
| 2022 |
Casein kinase 2 (CK2) directly interacts with USP13 and phosphorylates it at Thr122, promoting the stability of USP13 protein. Thr122 phosphorylation is important for ovarian cancer cell proliferation. |
Co-IP, kinase assay, phospho-specific detection, phosphorylation-deficient and phosphomimetic mutants, cell proliferation assays |
Cancers |
Medium |
36612196
|
| 2022 |
USP13 modulates the stability of the APC/C adaptor CDH1. USP13 binds CDH1 and its overexpression increases CDH1 levels while depletion decreases them, establishing a USP13-CDH1-Aurora B regulatory axis for cell cycle progression. |
Co-IP, Western blot after USP13 overexpression/siRNA/shRNA, cell cycle analysis |
Molecular biology reports |
Low |
35397714
|
| 2023 |
USP13 deubiquitinates and stabilizes cyclin D1 by physically binding to its N-terminal domain and removing K48-linked (but not K63-linked) polyubiquitin chains, promoting G1/S cell cycle progression and proliferation in gastric cancer cells. |
Co-IP, deubiquitination assay with K48/K63 ubiquitin mutants, USP13 KO/overexpression, cell cycle analysis, in vivo xenograft |
Oncogene |
High |
37311811
|
| 2023 |
USP13 directly binds p62/SQSTM1 and removes ubiquitin at Lys7 (K7) of the PB1 domain. This deubiquitination enhances p62 protein stability and facilitates p62 oligomerization, resulting in increased selective autophagy and degradation of Keap1, thereby promoting Nrf2 activation and antioxidant gene expression. |
Co-IP, site-directed mutagenesis (K7), ubiquitination assay, autophagy flux assays, Keap1/Nrf2 pathway readouts |
Free radical biology & medicine |
Medium |
37776917
|
| 2023 |
USP13 interacts with and deubiquitinates METTL3 at K488 by removing K48-linked ubiquitin chains, stabilizing METTL3 and increasing global m6A abundance in osteosarcoma cells, which promotes ATG5 mRNA stability and autophagy-associated malignancy. |
Co-IP, deubiquitination assay with K48 ubiquitin mutants, RNA-seq, m6A-IP sequencing, USP13 inhibitor in xenograft |
International journal of biological sciences |
Medium |
37151889
|
| 2023 |
USP13 interacts with Twist1 and specifically cleaves K48-linked polyubiquitin chains from Twist1 induced by FBXL14, stabilizing Twist1 and promoting breast cancer cell migration and invasion. Twist1 in turn inhibits USP13 transcriptional activity, forming a negative feedback loop. |
Co-IP, GST pulldown, deubiquitination assay with K48-specific ubiquitin, USP13 KD/OE, migration/invasion and in vivo lung metastasis assays, luciferase reporter for USP13 promoter |
Cellular oncology |
Medium |
36732432
|
| 2023 |
KRAS drives expression of USP13 through the transcription factor RREB1. Elevated USP13 removes K63-linked polyubiquitination of β-catenin at lysine 508, enhancing binding of β-catenin to TCF4 and promoting KRAS-mutant NSCLC metastasis. |
ChIP/reporter assays for RREB1-USP13 axis, Co-IP, K63-specific deubiquitination assay, K508 site mutation, metastasis assays in vitro and in vivo |
Cell reports |
Medium |
38043062
|
| 2023 |
USP13 interacts with and deubiquitinates SARM1 (axon degeneration executor). USP13 deubiquitination of SARM1 increases the inhibitory interaction between SARM1's N-terminal ARM domain and C-terminal TIR domain, suppressing SARM1 activation and delaying injury-induced axon degeneration. Enzyme-dead USP13 fails to protect injured axons. |
Proximity labeling/proteomics to identify SARM1 interactome, overexpression of WT vs. enzyme-dead USP13, domain interaction assays, axon degeneration assays |
Life medicine |
Medium |
39872893
|
| 2023 |
USP13 deubiquitinates Beclin 1 (distinct from the earlier finding that Beclin1 regulates USP13). In aged Usp13-deficient mice, impaired Beclin 1 deubiquitination leads to insufficient autophagic activity and increased vulnerability to bleomycin-induced lung fibrosis. |
USP13-deficient aged mice, Beclin 1 deubiquitination assay, Beclin 1 overexpression rescue, bleomycin fibrosis model |
American journal of respiratory cell and molecular biology |
Medium |
36150040
|
| 2020 |
USP13 protein is degraded in response to LPS in Kupffer cells via the ubiquitin-proteasome system. LPS increases USP13 polyubiquitination and reduces its protein stability (not transcription). Inhibition of c-Jun N-terminal kinase (JNK) attenuates USP13 degradation, indicating JNK-dependent new protein synthesis is necessary for USP13 degradation. A catalytically inactive USP13 shows similar degradation, indicating the mechanism is activity-independent. |
LPS treatment, proteasome/lysosome inhibitor experiments, JNK inhibitor, cycloheximide chase, catalytic mutant USP13 |
Journal of cellular physiology |
Medium |
33169399
|
| 2022 |
USP13 deubiquitinates and stabilizes ATG5 in gastrointestinal stromal tumor cells (also confirmed in AML). PAK1-mediated phosphorylation of ATG5 enhances the ATG5-USP13 interaction. |
Co-IP, deubiquitination assay, PAK1 inhibition, USP13 knockdown, autophagy flux and tumor growth assays |
Cell death and differentiation / Tissue & cell |
Medium |
36528756 39216303
|
| 2024 |
USP13 interacts with and deubiquitinates NFE2L2/NRF2, upregulating NRF2 protein levels. In KRAS-mutant lung adenocarcinoma, USP13 depletion promotes an autophagy-to-ferroptosis switch through the NRF2-SQSTM1/p62-KEAP1 axis. |
DUB screen (85 DUBs), Co-IP, deubiquitination assay, USP13 KD in vitro and xenograft, autophagy/ferroptosis markers |
Autophagy |
Medium |
39360581
|
| 2024 |
USP13 interacts with TAK1 (transforming growth factor β-activated kinase 1) and inhibits K63-linked ubiquitination and phosphorylation of TAK1, thereby dampening downstream inflammatory pathways (NF-κB) and promoting insulin signaling in the context of NAFLD. |
Co-IP, ubiquitination assay (K63-specific), TAK1 inhibitor rescue, USP13 overexpression/KO mice, NAFLD models |
Journal of translational medicine |
Medium |
39033101
|
| 2024 |
USP13 deubiquitinates ATG7 (autophagy-related 7) by preventing its degradation, stabilizing ATG7 protein and promoting ferroptosis in chicken granulosa cells. |
USP13 overexpression/knockdown, Co-IP, deubiquitination assay, ferroptosis markers (GSH, lipid peroxidation, iron) |
Poultry science |
Low |
39214053
|
| 2023 |
USP13 interacts with FASN (fatty acid synthase) and enhances FASN protein stability, with this USP13-FASN axis required for SCLC cancer stem cell maintenance and lipogenesis. Effect requires enzymatic activity of USP13 (inactive mutant cannot rescue). |
Co-IP, protein stability assay, WT vs. inactive USP13 rescue, sphere formation assay, in vivo tumor growth |
Frontiers in oncology |
Medium |
35898882
|
| 2021 |
USP13 selectively stabilizes mutant EGFR (but not wild-type EGFR) in a peptidase-independent manner by counteracting the action of Cbl family E3 ubiquitin ligases. |
Unbiased high-throughput siRNA screen, USP13 KD, Cbl ligase functional assays, mutant vs. WT EGFR stability, in vitro and in vivo sensitivity assays |
International journal of cancer |
Medium |
33210294
|
| 2025 |
USP13 stabilizes NLRP3 independently of its deubiquitinating enzyme activity by competing with E3 ligase TRIM31 to interact with NLRP3, preventing TRIM31-mediated ubiquitination of NLRP3 at K192 and K496, thereby inhibiting proteasomal degradation of NLRP3 and promoting NLRP3 inflammasome assembly and activation. |
Co-IP, ubiquitination assay with site-specific NLRP3 K192/K496 mutants, USP13 KO in human and mouse macrophages, DUB-dead mutant analysis, inflammasome activation readouts, peritonitis mouse model |
Science advances |
High |
41004574
|
| 2025 |
USP13 deubiquitinates STAT1, reducing its degradation. In cardiomyocytes, USP13 promotes STAT1-targeted Nppb gene transcription and enhances mitochondrial function. Cardiomyocyte-specific Usp13 knockout aggravates pressure overload-induced cardiac hypertrophy, while AAV9-mediated USP13 overexpression has therapeutic effects. |
Interactome analysis identifying STAT1 as substrate, Co-IP, deubiquitination assay, cardiomyocyte-specific KO mice (TAC/Ang II models), AAV9 overexpression |
Nature communications |
High |
40593642
|
| 2025 |
USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes its autolysosome-related degradation (rather than stabilization), alleviating cardiomyocyte inflammation in doxorubicin-induced cardiotoxicity. Cardiomyocyte-specific USP13 KO exacerbates cardiotoxicity while overexpression mitigates it. |
RNA-seq, Co-IP, deubiquitination assay, cardiomyocyte-specific KO mice, AAV9 overexpression, autophagy flux assays |
Acta pharmaceutica Sinica. B |
Medium |
40487656
|
| 2025 |
USP13 deubiquitinates SMAD3 by removing K48-linked ubiquitin chains at K13 of SMAD3's MH2 domain (USP13 C345 is the catalytic cysteine involved), stabilizing SMAD3 and enhancing its transcriptional activity for profibrotic genes, thereby promoting hepatic stellate cell activation and liver fibrosis. |
Co-IP/MS substrate identification, domain mapping (MH2 domain), K13 site-specific ubiquitination assay, C345 catalytic mutant, HSC-specific AAV-mediated KD, CCl4 and BDL fibrosis mouse models |
Hepatology international |
Medium |
40719972
|
| 2025 |
USP13 deubiquitinates WWP1 E3 ligase by removing K29- and K48-linked polyubiquitin chains, stabilizing WWP1 via the ubiquitin-proteasome pathway. The transcription factor YY1 activates USP13 transcription and also upregulates WWP1 through USP13. |
Co-IP, mass spectrometry, ubiquitination assay with K29/K48-specific chains, ChIP and luciferase assay for YY1-USP13 promoter interaction, in vivo xenograft |
Cellular & molecular biology letters |
Medium |
40319251
|
| 2025 |
USP13 deubiquitinates NLRP3 at K557 by removing K63-linked ubiquitin chains, inhibiting NLRP3-ASC interaction and ASC polymerization, thereby inhibiting NLRP3 inflammasome activation and alleviating pyroptosis in cardiomyocytes in diabetic cardiomyopathy. |
Co-precipitation + LC-MS/MS substrate identification, K557 site-specific ubiquitination assay, K63-specific ubiquitin chains, cardiomyocyte-specific KO mice (type I and II diabetic), AAV9 overexpression, NLRP3-deficient rescue |
Cell death and differentiation |
High |
41206387
|
| 2025 |
USP13 stabilizes ACLY (ATP citrate lyase) via K48-specific deubiquitination at K726, preventing proteasomal degradation. Under hypoxia, HIF-1α transcriptionally upregulates USP13 by binding its promoter, creating a hypoxia-USP13-ACLY axis that drives ferroptosis resistance and immune evasion in HCC. |
Co-IP, K48-specific deubiquitination assay at K726, HIF-1α ChIP/promoter assay, USP13 inhibitor (2-Met) in PDOs and xenograft, scRNA-seq, flow cytometry |
Cell death discovery |
Medium |
41330897
|
| 2025 |
USP13 interacts with ALDOA (fructose-bisphosphate aldolase A) via its USP domain and regulates K48-linked deubiquitination and stability of ALDOA at K13, preventing its proteasomal degradation and thereby restraining ferroptosis in cardiomyocytes following myocardial infarction. |
Co-IP, K48-specific ubiquitination assay at K13, USP13-deficient mice + cardiac-specific AAV9 overexpression, MI surgery model, ferroptosis markers |
Redox biology |
Medium |
41496210
|
| 2025 |
USP13 interacts with and stabilizes SOCS1 by mediating K63-linked deubiquitination of SOCS1, thereby restraining excessive JAK-STAT pathway activation. USP13 knockout promotes αPD-1 resistance in CRC tumors and reduces CD8+ T-cell infiltration. |
Co-IP, K63-specific ubiquitination assay, USP13 KO syngeneic mouse model, flow cytometry for CD8+ T cells, JAK-STAT pathway readouts |
Oncogene |
Medium |
42000926
|
| 2025 |
USP13 interacts with and deubiquitinates PARP1, stabilizing PARP1 via the ubiquitin-proteasome pathway and promoting PARP1-mediated DNA damage repair in multiple myeloma cells. |
Mass spectrometry, Co-IP, in vitro ubiquitination assay, USP13 KD/OE, PARP1 stability assay, MM xenograft and patient-derived tumor xenograft models |
Basic & clinical pharmacology & toxicology |
Medium |
40151951
|
| 2025 |
TDP-43 regulates USP13 RNA splicing; TDP-43 knockdown induces aberrant splicing of USP13 and blocks USP13 rhythmic expression, enhancing BMAL1 ubiquitination and disrupting circadian clock gene expression. |
TDP-43 knockdown in vivo and in vitro, RNA splicing analysis of USP13, BMAL1 ubiquitination assay, circadian wheel behavior tests |
The Journal of cell biology |
Medium |
40202498
|
| 2025 |
USP13 regulates MDM2 protein by targeting its K63-linked polyubiquitination. Overexpression of USP13 reduces MDM2 levels (degradation prevented by MG132) and promotes cell senescence; knockdown increases MDM2 levels. This places USP13 in a lung aging/senescence pathway. |
USP13 KO mice, KD/OE in human cell lines, MDM2 stability assay with MG132, K63-specific ubiquitination assay, β-galactosidase senescence assay |
Life sciences |
Medium |
37634814
|
| 2025 |
USP13 interacts with GRP78 and removes K63-linked ubiquitin at K327 of GRP78, attenuating ER stress-induced apoptosis and maintaining intestinal barrier integrity. Intestinal epithelial-specific USP13 KO exacerbates DSS-induced colitis. |
Co-IP, site-specific K63 deubiquitination assay at K327, intestinal epithelial Usp13 KO mice, AAV9 rescue, DSS colitis model, apoptosis/ER stress markers |
Advanced science |
Medium |
40679368
|
| 2026 |
USP13 interacts with KDM3A histone demethylase and specifically removes K63-linked ubiquitin chains from KDM3A; this indirectly promotes K48-linked polyubiquitination-dependent proteasomal degradation of KDM3A in the cytoplasm, inhibiting bladder cancer metastasis. |
Co-IP, K63/K48-specific ubiquitination assay, USP13 KD, bladder-injected liver metastasis xenograft model |
Oncogene |
Medium |
41872693
|
| 2025 |
USP13 stabilizes CMAS (cytidine monophosphate N-acetylneuraminic acid synthetase) by specifically cleaving K48-linked polyubiquitin chains from CMAS, enhancing melanogenic capacity. The transcription factor FOXO4 represses USP13 expression through direct promoter interaction, establishing a FOXO4-USP13-CMAS regulatory axis in melanogenesis. |
Proteome-ubiquitinome analysis of USP13-overexpressing melanocytes, Co-IP, K48-specific deubiquitination assay, FOXO4 luciferase reporter + EMSA |
Cellular signalling |
Medium |
40876694
|
| 2026 |
USP13 knockdown reduces insoluble TDP-43 levels and reduces cell death in primary rat motor neurons; knockdown also improves locomotor deficits in C. elegans ALS models, identifying USP13 as a modifier of TDP-43-induced aggregation and cytotoxicity. |
Inducible mutant TDP-43 HEK293 model, discovery proteomics via RAD23A KD, USP13 KD in HEK293 and primary rat neurons, TDP-43 solubility assay, C. elegans locomotor assay |
The Journal of neuroscience |
Medium |
41371952
|
| 1998 |
ISOT-3 (USP13) was identified as a novel isopeptidase T gene on human chromosome 3q26.2–q26.3, showing 54.8% amino acid identity to ISOT-1 (USP5). The exonic organization is highly conserved with ISOT-1, with USP13 having significantly larger introns (gene ≥90 kb vs 15 kb for ISOT-1), suggesting common ancestry but potentially different substrate specificities. |
Genomic sequencing, Northern blot analysis of tissue expression, comparative genomic organization |
Gene |
Low |
9841226
|