| 1999 |
Recombinant USP15 demonstrated ubiquitin-specific protease activity against engineered linear fusions of ubiquitin to beta-galactosidase and glutathione S-transferase, and can cleave the ubiquitin-proline bond. USP15 protein consists of 952 amino acids and contains conserved Cys and His boxes present in all UBP family members. |
In vitro deubiquitinase activity assay with recombinant protein against linear ubiquitin fusion substrates |
Genomics |
High |
10444327
|
| 2005 |
USP15 co-purifies with the human COP9 signalosome (CSN) complex. A novel zinc finger in USP15 is essential for cleavage of poly-ubiquitin chains; mutation of a single conserved cysteine in the Zn-binding motif abolishes poly-Ub substrate degradation and reduces tetra-Ub binding. Wild-type but not Zn-finger-mutant USP15 stabilizes the E3 ligase Rbx1 by reversing its poly/autoubiquitination. |
Co-purification, pulldown with tetra-Ub, site-directed mutagenesis, cotransfection ubiquitination assay |
Current biology : CB |
High |
16005295
|
| 2009 |
USP15 stabilizes APC (adenomatous polyposis coli) protein in the context of the COP9 signalosome-associated complex. Knockdown of USP15 or overexpression of a catalytically inactive USP15 mutant accelerates APC proteolysis, demonstrating that CSN-associated USP15 protects APC from ubiquitin-mediated degradation. |
siRNA knockdown, overexpression of catalytically inactive mutant, Western blot for APC stability |
Journal of molecular biology |
Medium |
19576224
|
| 2009 |
USP15 interacts with HPV16 E6 protein (identified by tandem affinity purification). Overexpression of USP15 increases E6 protein levels and siRNA-mediated knockdown of USP15 decreases E6 protein levels, implicating USP15 in stabilization of E6 through deubiquitylation. |
Tandem affinity purification, siRNA knockdown, overexpression, Western blot |
Journal of virology |
Medium |
19553310
|
| 2011 |
USP15 is a deubiquitylating enzyme for receptor-activated SMADs (R-SMADs: SMAD1, 2, 3). USP15 primarily opposes R-SMAD monoubiquitylation at DNA-binding domains, which normally prevents promoter recognition. USP15 is required for TGF-β and BMP responses in mammalian cells and Xenopus embryos and is necessary for SMAD complex occupancy of endogenous target promoters. |
siRNA knockdown, overexpression, ChIP, in vitro deubiquitylation assays, Xenopus embryo knockdown |
Nature cell biology |
High |
21947082
|
| 2011 |
Crystal structure of the USP15 N-terminal DUSP and UBL domains at 1.5 Å resolution reveals an 80 Å elongated arrangement with the DU domains aligned in tandem, connected through a β-hairpin (DU finger) that forms an intricate hydrogen-bonding network. The UBL domain is monomeric in solution and unlikely to act as a ubiquitin mimic. |
X-ray crystallography, analytical ultracentrifugation, SAXS, gel filtration |
Biochemistry |
High |
21848306
|
| 2012 |
USP15 binds to the SMAD7-SMURF2 complex and deubiquitinates and stabilizes type I TGF-β receptor (TβR-I), leading to enhanced TGF-β signaling. Identified via functional RNAi screen; downregulation or inhibition of USP15 decreases TGF-β activity in patient-derived orthotopic mouse glioblastoma models. |
Functional RNAi screen, Co-IP, in vitro deubiquitylation, orthotopic mouse model with patient-derived cells |
Nature medicine |
High |
22344298
|
| 2012 |
USP15 interacts with the E3 ligase BRAP/IMP through the N-terminal DUSP-UBL domain of USP15 and the coiled-coil region of BRAP. USP15 opposes BRAP autoubiquitylation and stabilizes BRAP protein through its catalytic activity. USP15 depletion destabilizes BRAP via proteasomal degradation, reduces CRAF levels, and decreases MAPK signaling amplitude in response to EGF and PDGF. |
Co-IP, domain mapping, catalytically inactive mutant rescue, siRNA knockdown, Western blot, EGF/PDGF stimulation assays |
The Journal of biological chemistry |
Medium |
23105109
|
| 2013 |
USP15 stabilizes newly synthesized REST (RE1-silencing transcription factor) by antagonizing its polyubiquitylation in a catalytic-activity-dependent manner. USP15 specifically promotes de novo REST synthesis (associates with polysomes) rather than protecting pre-existing REST, and is required for rapid accumulation of newly synthesized REST at mitotic exit. |
siRNA screening, polysome fractionation, cycloheximide chase, ubiquitination assays, cell cycle analysis |
Cell cycle (Georgetown, Tex.) |
Medium |
23708518
|
| 2013 |
USP15 specifically deubiquitinates Keap1 (not Nrf2 directly), which promotes incorporation of deubiquitinated Keap1 into the Keap1-Cul3-E3 ligase complex, enhancing complex stability and enzymatic activity. This leads to increased Nrf2 protein degradation and reduced Nrf2 target gene expression, suppressing the antioxidant response. |
In vitro deubiquitylation assay, co-immunoprecipitation, siRNA knockdown, Western blot, reporter gene assays |
Molecular cell |
High |
23727018
|
| 2014 |
USP15 stabilizes the E3 ubiquitin ligase MDM2 through deubiquitination. USP15-stabilized MDM2 negatively regulates T cell activation by targeting NFATc2 for degradation. USP15 deficiency promotes T cell activation and enhances antitumor T cell responses. USP15 also stabilizes MDM2 in cancer cells to regulate p53 function. |
Co-IP, in vitro deubiquitylation assay, USP15 knockout mice, T cell activation assays, tumor challenge models |
Nature immunology |
High |
24777531
|
| 2014 |
USP15 opposes Parkin-mediated mitophagy by counteracting Parkin-mediated mitochondrial ubiquitination. USP15 does not affect Parkin ubiquitination status or Parkin translocation to mitochondria, but specifically counteracts ubiquitination of outer mitochondrial membrane proteins. A catalytically inactive version of USP15 does not oppose mitophagy. Knockdown of USP15 rescues the mitophagy defect in PD patient fibroblasts with PARK2 mutations. |
siRNA knockdown, catalytically inactive mutant, mitophagy assays, patient fibroblasts, Drosophila parkin RNAi rescue |
Human molecular genetics |
High |
24852371
|
| 2014 |
USP15 deubiquitylates TRIM25, preventing LUBAC-dependent K48-linked polyubiquitylation and proteasomal degradation of TRIM25. USP15 was identified as an interaction partner of TRIM25 by protein purification and mass spectrometry. Wild-type but not catalytically inactive USP15 reduces K48-linked ubiquitylation of TRIM25, stabilizes it, and enhances TRIM25- and RIG-I-dependent type I IFN production. |
Affinity purification, mass spectrometry, Co-IP, siRNA knockdown, overexpression of catalytically inactive mutant, IFN reporter assays, viral replication assays |
Science signaling |
High |
24399297
|
| 2014 |
USP15 identifies and deubiquitylates monoubiquitinated histone H2B (ubH2B). In the nucleus, USP15 indirectly associates with the ubH2B E3 ligase RNF20/RNF40, and directly associates with SART3 (TIP110/p110). SART3 acts as a histone chaperone that enhances USP15 binding to ubH2B and facilitates deubiquitination of free ubH2B histones. |
Affinity purification with nonhydrolyzable ubH2B mimic, Co-IP, in vitro deubiquitination assay with SART3 |
The Journal of biological chemistry |
High |
24526689
|
| 2014 |
USP15 deubiquitylates ALK3/BMPR1A (BMP type I receptor) by interacting with SMAD6, an inhibitory SMAD that recruits E3 ubiquitin ligases to ALK3. USP15 reduces K48-linked polyubiquitylation of ALK3, enhances BMP-induced SMAD1 phosphorylation, and promotes BMP target gene transcription. Loss of USP15 inhibits BMP-induced osteoblast differentiation in myoblasts and modulates BMP signaling in Xenopus embryos. |
Co-IP, RNAi depletion, ubiquitination assay, SMAD1 phosphorylation assay, BMP target gene reporter, Xenopus embryo experiments |
Open biology |
High |
24850914
|
| 2015 |
USP15 deubiquitinates SMURF2 at Lys734, a residue required for SMURF2 catalytic activity. This results in enhanced TβR-I stability and downstream TGF-β pathway activation. Proteomic analysis identified SMURF2 as a USP15 target in addition to TβR-I. |
Proteomic mass spectrometry, Co-IP, in vitro deubiquitination assay, mutational analysis of Lys734 |
Scientific reports |
Medium |
26435193
|
| 2015 |
USP4, USP15, and USP11 arose by whole genome and small-scale duplications in vertebrate evolution. Viability of mice is contingent on a functional copy of either USP4 or USP15 (genetic redundancy established by cross-breeding mice with inactivating mutations in both genes). |
Phylogenetic and syntenic reconstruction, genetic crosses of Usp4/Usp15 mutant mice |
BMC evolutionary biology |
Medium |
26503449
|
| 2016 |
USP15 co-expressed with and functionally acts together with the E3 ubiquitin ligase TRIM25 to positively regulate type I interferon responses. The USP15L749R mutation in mice dampens type I interferon responses in brain and hematopoietic cells, protecting against experimental cerebral malaria and EAE neuroinflammation. |
ENU-mutagenesis mouse model, immunophenotyping, RNA sequencing, in situ neuroinflammation models |
Nature immunology |
High |
27721430
|
| 2016 |
TGF-β promotes translation of USP15 through activation of mTOR via the PI3K/AKT pathway. Upregulated USP15 then binds to and stabilizes p53 through deubiquitination in U2OS and HEK293 cells. |
Co-IP, ubiquitination assay, PI3K/AKT/mTOR pathway inhibitors, Western blot |
Oncogene |
Medium |
27893708
|
| 2016 |
Structural basis for SART3 recruitment of USP15: crystal structures of SART3 alone and in complex with USP15 DUSP-UBL domain at 2.0 and 3.0 Å respectively reveal SART3 contains 12 HAT repeats in two subdomains, dimerizes through HAT-C concave surface, and binds USP15 in a novel bipartite mode on the HAT-C convex surface. USP15 binds SART3 ~20-fold more tightly than USP4. |
X-ray crystallography, isothermal titration calorimetry, mutagenesis |
The Journal of biological chemistry |
High |
27255711
|
| 2017 |
USP15, together with its substrate-targeting factor SART3, deubiquitinates PRP31 (a U4 snRNP component). PRP31 is modified with K63-linked ubiquitin chains by the PRP19 complex. USP15-SART3 forms a complex with USP4, and this ternary complex also deubiquitinates PRP3. The ubiquitination/deubiquitination status of PRP31 regulates its interaction with U5 snRNP component PRP8, required for efficient splicing of chromosome segregation-related genes. |
Co-IP, in vitro deubiquitination assay, ubiquitin linkage-specific analysis, splicing assays |
Nucleic acids research |
High |
28088760
|
| 2017 |
The long isoform of USP15 (containing exon 7-encoded serine-rich stretch) preferentially recognizes and deubiquitylates mysterin/RNF213 (a large ubiquitin ligase associated with moyamoya disease), while the short isoform does not. Exon 7 skipping alters substrate specificity of USP15 isoforms, with only partially overlapping interactomes. |
Isoform-specific pulldown, deubiquitylation assay, mass spectrometry interactome comparison |
Scientific reports |
Medium |
28276505
|
| 2017 |
USP15 interacts with and deubiquitinates SLIM1 (skeletal muscle LIM protein 1), increasing SLIM1 protein levels. Cardiac-specific overexpression of USP15 in transgenic mice induces cardiac remodeling with elevated heart weight/body weight ratios and upregulation of fetal gene markers, associated with increased endogenous SLIM1 levels. |
Cell-free binding, co-immunoprecipitation, in vitro deubiquitination, transgenic mouse model |
Biochemical and biophysical research communications |
Medium |
21219870
|
| 2018 |
Crystal structure of the USP15 catalytic core domain reveals a canonical USP fold (finger, palm, thumb regions) but with a misaligned catalytic triad — catalytic cysteine ~10 Å from catalytic histidine, an inactive configuration. Active-site loops are flexible, creating a largely open ubiquitin tail-binding channel. USP15 displays lower monoubiquitin affinity than paralog USP4. Mitoxantrone weakly inhibits USP15 and binds the S1' site. |
X-ray crystallography, isothermal titration calorimetry, enzyme inhibition assay |
The Journal of biological chemistry |
High |
30228188
|
| 2018 |
USP15 deubiquitylates BARD1 BRCT domain upon recruitment to DNA double-strand breaks (DSBs) by MDC1. Recruitment requires the FHA domain of MDC1 and phosphorylated Ser678 of USP15. USP15-mediated BARD1 deubiquitylation promotes BARD1-HP1γ interaction, retaining BRCA1/BARD1 at DSBs and promoting homologous recombination (HR). USP15 knockout mice exhibit genomic instability. |
Co-IP, phospho-mutant analysis, BARD1 deubiquitylation assay, HR assay, USP15 KO mice |
Nature communications |
High |
30874560
|
| 2018 |
USP15 deubiquitylates topoisomerase IIα (TOP2A), and USP15 depletion leads to decreased TOP2A accumulation, formation of anaphase chromosome bridges, and micronuclei indicating genome instability. Both USP15 isoforms move from cytoplasm to nucleus at prophase; isoform-1 is phosphorylated on S229 at mitotic entry and an S229D phospho-mimetic cannot rescue TOP2A accumulation or the micronuclei phenotype, demonstrating isoform-specific phospho-regulation. |
siRNA depletion, phospho-mutant rescue, live-cell imaging, cell cycle analysis, ubiquitination assay |
Oncogene |
High |
29429988
|
| 2018 |
HPV16 E6 oncoprotein forms a complex with TRIM25 and USP15 in human cells. In the presence of E6, K48-linked ubiquitination of TRIM25 is markedly increased and TRIM25 degradation is enhanced, and E6 inhibits TRIM25-mediated K63-linked ubiquitination of RIG-I and its CARD-dependent interaction with MAVS. |
Co-IP, ubiquitination assay, CRISPR-Cas9 knockout in keratinocytes, IFN reporter assay |
Journal of virology |
Medium |
29263274
|
| 2019 |
Ubiquitin variants (UbVs) targeting either the USP15 catalytic domain or each of three adaptor domains (including the DUSP domain) inhibit USP15 catalytic activity. A linear dimer UbV targeting both DUSP and catalytic domains shows enhanced specificity. Crystal structures show three distinct UbVs bind the catalytic domain and lock the active site in a closed, inactive conformation; one UbV forms an unusual strand-swapped dimer binding two DUSP domains simultaneously. In cells, UbVs inhibit deubiquitination of SMURF2 and TRIM25 substrates. |
Protein engineering (UbVs), X-ray crystallography, cell-based deubiquitination assays, TGF-β pathway assays |
Structure (London, England : 1993) |
High |
30713027
|
| 2019 |
The ER-located E3 ligase Hrd1 interacts with USP15 and ubiquitinates it. Unlike classical Hrd1 substrates, USP15 is not degraded but loses its deubiquitinating activity toward IκBα, resulting in excessive NF-κB activation. This represents a non-canonical Hrd1 function linking ER-plasma membrane signaling during bacterial TLR4 responses. |
E3 ligase screen (>280 ligases), Co-IP, ubiquitination assay, IκBα deubiquitination assay, macrophage-specific Hrd1 KO mice, LPS-sepsis model |
Nature microbiology |
High |
31477895
|
| 2019 |
USP15 phosphorylation at Thr149 and Thr219 (identified by nuclear-cytoplasmic fractionation and mass spectrometry) occurs in the cytoplasm. The phosphorylation status alters interaction with SART3, leading to nuclear localization and deubiquitinating activity toward spliceosomal substrate PRP31. Treatment with CDK inhibitor purvalanol A induces nuclear translocation of USP15. |
Subcellular fractionation, mass spectrometry, phospho-mutant analysis, Co-IP, in vitro deubiquitination assay |
Journal of molecular biology |
Medium |
31330151
|
| 2019 |
USP15 deubiquitylates and stabilizes HECTD1 E3 ubiquitin ligase in glioblastoma cells. USP15 expression attenuates canonical WNT pathway activity in a manner dependent on HECTD1; depletion of USP15 reduces HECTD1 protein levels. USP15 interaction with HECTD1 was identified by mass spectrometry. |
Mass spectrometry protein network analysis, Co-IP, ubiquitination assay, WNT reporter assay, soft agar colony formation |
Oncotarget |
Medium |
29299163
|
| 2020 |
USP15 deubiquitylates and inactivates TET2 by removing K1299-linked monoubiquitin, which normally promotes TET2 activity. Deletion of Usp15 in melanoma cells stimulates chemokine expression and tumor-infiltrating lymphocyte accumulation in a TET2-dependent manner, leading to increased immunotherapy response. |
Co-IP, in vitro deubiquitylation assay, gene expression profiling, Usp15 KO melanoma model, immunotherapy challenge |
Science advances |
High |
32948596
|
| 2020 |
USP15 potentiates NF-κB activation upon TNFα or IL-1β stimulation by stabilizing TAB2 and TAB3 through different mechanisms: (1) catalytic-activity-dependent deubiquitination of K48-linked TAB2 ubiquitin chains; (2) catalytic-activity-independent inhibition of lysosome-mediated TAB2 degradation; (3) catalytic-activity-independent inhibition of NBR1-mediated selective autophagic TAB3 degradation. |
Co-IP, ubiquitination assay, overexpression/knockdown of USP15, catalytically inactive mutant, NF-κB reporter, lysosome/autophagy inhibitor experiments |
The FEBS journal |
Medium |
31903660
|
| 2020 |
UBE2S recruits USP15 to TBK1 to remove K63-linked polyubiquitin chains from TBK1, thereby inhibiting TBK1 activation and type I IFN production. UBE2S-mediated inhibition of IFN is independent of its E2/E3 enzymatic activity but requires USP15 recruitment. |
Co-IP, ubiquitination assay (K63 linkage-specific), USP15 knockdown, viral replication assays in vitro and in vivo |
Cell reports |
Medium |
32814047
|
| 2020 |
TIFAB regulates USP15 ubiquitin hydrolase activity (acts as an effector/activator of USP15). Expression of TIFAB in hematopoietic stem/progenitor cells permits USP15 signaling to substrates MDM2 and KEAP1, mitigating p53 expression. TIFAB-deficient HSPCs exhibit compromised USP15 signaling and are sensitized to hematopoietic stress by derepression of p53. |
Proteomics, co-IP, USP15 activity assays, genetic knockdown/overexpression in HSPCs, MLL-AF9 leukemia model |
Cell reports |
Medium |
32101751
|
| 2020 |
USP15 interacts with and stabilizes FUS (fused in sarcoma), a known DNA repair factor, in leukemia cells. USP15 is essential for HSC maintenance in vitro and in vivo (transplantation and Usp15 KO mice), and its depletion in leukemia cells impairs expansion and increases genotoxic stress. |
Co-IP, shRNA in vivo screen, Usp15 KO mice, transplantation assays, genotoxic stress assays |
Cell reports |
Medium |
33378683
|
| 2020 |
USP15 deubiquitinates CARD9, constitutively associating with it and removing TRIM62-deposited ubiquitin marks. USP15 knockdown and knockout specifically enhance CARD9-dependent C-type lectin receptor (CLR) signaling in mouse and human immune cells. |
Co-IP, ubiquitination assay, siRNA knockdown, CRISPR KO, CLR signaling assays |
ImmunoHorizons |
Medium |
33093067
|
| 2021 |
USP15 deubiquitinates and stabilizes glutamine synthetase (GS) and CRL4CRBN neosubstrates IKZF1, IKZF3, CK1-α, RNF166, GSPT1, and BRD4 by antagonizing CRL4CRBN-mediated ubiquitylation. USP15 is highly expressed in IMiD-resistant myeloma cells and depletion sensitizes these cells to lenalidomide. |
Ubiquitination assays, Western blot for substrate stability, siRNA depletion, lenalidomide sensitivity assays |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
34583995
|
| 2021 |
USP15 deubiquitinates and stabilizes p53-R175H gain-of-function mutant through a lysosome-mediated pathway. USP15 is established as a selective upstream regulator of p53-R175H stability distinct from wild-type p53 regulation. |
Chemical genetic approach (MCB-613), siRNA knockdown, CRISPR, ubiquitination assay, lysosome pathway assays |
Nature communications |
Medium |
29593334
|
| 2021 |
USP15 deubiquitinates TUT1 (terminal uridylyl transferase 1) and causes redistribution of TUT1 from nucleolus to nucleoplasm, stabilizing U6 snRNA. Usp15 knockout mice show impaired motor ability and unconventional cerebellar formation. Inhibition of the USP15-TUT1 cascade triggers mild chronic ER stress. |
Co-IP, ubiquitination assay, immunofluorescence localization, Usp15 KO mice, U6 snRNA stability assay, ER stress markers |
Molecular and cellular biology |
Medium |
32839293
|
| 2021 |
USP15 deubiquitinates and stabilizes ERα (estrogen receptor alpha) by removing K48-linked ubiquitin, promoting ERα+ breast cancer cell proliferation. USP15 knockdown reduces ERα protein levels and enhances tamoxifen antitumor activity. |
Co-IP, ubiquitination assay (K48 linkage-specific), siRNA knockdown, in vitro and in vivo proliferation assays |
Cell death & disease |
Medium |
33771975
|
| 2021 |
USP15 deubiquitinates BECN1 (Beclin-1), interacting with BECN1 but not TRAF6, thereby attenuating TRAF6-BECN1 axis-driven autophagy induction. USP15-knockout lung cancer cells show increased cancer migration and invasion with enhanced autophagy in response to TLR4 stimulation. |
Co-IP, deubiquitination assay, CRISPR-Cas9 KO cell lines, migration/invasion assays, autophagy assays |
Cell death & disease |
Medium |
35422093
|
| 2022 |
USP15 interacts with and promotes cGAS activation through deubiquitylation of cGAS and promotion of cGAS dimerization and liquid condensation via the USP15 intrinsic disordered region (IDR). In the absence of DNA, USP15 drives cGAS liquid condensation preparing cGAS for rapid DNA response. |
Co-IP, in vitro deubiquitylation assay, liquid-liquid phase separation assay, IDR deletion mutant analysis, cGAS activation assays |
Nucleic acids research |
Medium |
36243958
|
| 2022 |
Crystal structure of USP15 D1D2 catalytic domain in a catalytically competent conformation shows the active site can switch between active and inactive states independently of mitoxantrone binding. Mitoxantrone contributes to crystal packing by forming a stack of 12 molecules at the S1' site rather than inducing catalytic triad misalignment. |
X-ray crystallography (multiple crystal structures), comparative structural analysis |
Journal of structural biology |
High |
35605756
|
| 2023 |
USP15 interacts with and deubiquitinates PARP1 to promote its stability, stimulating DNA repair, genomic stability, and TNBC cell proliferation. ER inhibits USP15 expression at the promoter level, PR suppresses USP15 deubiquitinase activity, and HER2 abrogates the PARP1-USP15 interaction — explaining elevated PARP1 in TNBC where all three receptors are absent. |
Co-IP, in vitro deubiquitination assay, ChIP, USP15 activity assay in presence of PR, Co-IP in presence of HER2, TNBC cell proliferation/DNA repair assays |
Nature cancer |
High |
37012401
|
| 2023 |
The CRL3gigaxonin E3 ligase and USP15 form an opposing regulatory pathway governing destruction of neurofilament proteins NEFL and INA. USP15 antagonizes CRL3GIG-mediated ubiquitylation of NEFL and INA. A specific degron (NEFLL12) in neurofilament proteins is required for CRL3GIG binding; mutations in the GIG Kelch domain (L309R, R545C, C570Y) disrupt NEFL/INA binding causing accumulation of NF proteins as in giant axonal neuropathy. |
Ubiquitination assays, Co-IP, degron mapping, mutant GIG binding assays, proteasome degradation assays |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
37903270
|
| 2023 |
USP15 deubiquitinates SMYD3, stabilizing it and enabling H3K4me3-mediated transcriptional activation of CCL2. This promotes MDSC recruitment to tumors and immune evasion in colorectal cancer. USP15 inhibition improves anti-PD-1 efficacy in colorectal cancer models. |
Co-IP, deubiquitination assay, H3K4me3 ChIP, MDSC recruitment assays, orthotopic/metastatic colon tumor models, PD-1 blockade combination |
Cancer immunology research |
Medium |
40323348
|
| 2023 |
USP15 interacts with and deubiquitinates YAP1, inhibiting K48-linked ubiquitination of YAP1 and stabilizing it. USP15 also binds TAZ after hypoxia treatment. USP15 promotes PASMC proliferation and migration in a YAP1/TAZ-dependent manner, contributing to pulmonary vascular remodeling. |
Co-IP, ubiquitination assay (K48 linkage), USP15 knockdown (AAV-mediated in vivo), YAP1/TAZ rescue experiments, SuHx and MCT mouse models |
Experimental & molecular medicine |
Medium |
36635430
|
| 2024 |
USP15 deubiquitinates HKDC1 (a glycolytic regulator), inhibiting its ubiquitination-mediated degradation and thereby regulating glucose metabolism and glycolytic activity in gastric cancer cells. |
Co-IP, ubiquitination assay, USP15 knockdown/overexpression, glycolytic activity assays, xenograft models |
Journal of experimental & clinical cancer research : CR |
Medium |
39164728
|
| 2024 |
TRIM21 E3 ligase and USP15 antagonistically regulate ACSL4 protein stability in gastrointestinal stromal tumors (GISTs); TRIM21-mediated ubiquitination decreases ACSL4 while USP15 opposes this, and the balance determines imatinib sensitivity. |
Co-IP, ubiquitination assay, Western blot for ACSL4 stability, shRNA, xenograft model, GIST patient clinical data |
British journal of cancer |
Medium |
38182686
|