| 2002 |
USP11 localizes primarily to the nucleus in non-dividing cells and physically interacts with RanBPM (a RanGTP-binding protein) as confirmed by yeast two-hybrid and co-immunoprecipitation. USP11 deubiquitinates RanBPM in vitro and in vivo, protecting it from proteasomal degradation. |
Yeast two-hybrid, co-immunoprecipitation, in vitro/in vivo ubiquitination assay, pulse-chase analysis, immunofluorescence |
The Biochemical journal |
High |
12084015
|
| 2004 |
USP11 forms a specific complex with BRCA2 (identified by immunopurification-mass spectrometry) and can deubiquitinate BRCA2 in overexpression assays; a catalytically inactive USP11 mutant had no effect on BRCA2 ubiquitination or protein levels. Loss of USP11 function (dominant-negative or RNAi) increased cellular sensitivity to mitomycin C in a BRCA2-dependent manner, placing USP11 in the BRCA2 DNA damage repair pathway. |
Immunopurification-mass spectrometry, co-immunoprecipitation, catalytic mutant analysis, RNAi knockdown, cell survival assay |
Molecular and cellular biology |
High |
15314155
|
| 2007 |
USP11 knockdown attenuates IKKα expression at the transcriptional level and enhances NF-κB activation in response to TNFα. USP11 knockdown or IKKα knockdown abrogates p53 induction upon TNFα exposure; ectopic IKKα rescues p53 expression in USP11-silenced cells, establishing USP11 as an upstream regulator of an IKKα-p53 signaling pathway. |
siRNA knockdown, immunoblotting, reporter assays, rescue experiments |
The Journal of biological chemistry |
Medium |
17897950
|
| 2008 |
USP11 interacts with HPV-16 E7 (identified by yeast two-hybrid) and stabilizes E7 by removing ubiquitin chains and reducing degradation; a catalytically inactive USP11 mutant abolished deubiquitinating activity and returned E7 to normal degradation rates. USP11-mediated E7 stabilization modulated E7's effects on cell growth. |
Yeast two-hybrid, co-immunoprecipitation, in vitro deubiquitination assay, catalytic mutant analysis, immunoblotting |
The Journal of biological chemistry |
High |
18408009
|
| 2010 |
USP11 acts as a deubiquitinase for IκBα: recombinant USP11 catalyzes IκBα deubiquitination in vitro; USP11 overexpression inhibits IκBα ubiquitination and USP11 knockdown enhances TNFα-induced IκBα ubiquitination and NF-κB activation. A catalytically inactive USP11 mutant partially inhibits NF-κB activation, indicating a non-catalytic function as well. |
Proteomic approach (co-IP identification), in vitro deubiquitination assay, siRNA knockdown, overexpression, catalytic mutant analysis, reporter assay |
Cellular signalling |
High |
19874889
|
| 2010 |
USP11 participates in homologous recombination (HR) repair of DNA double-strand breaks. RNAi silencing of USP11 causes spontaneous DNA damage response activation, hypersensitivity to PARP inhibition and ionizing radiation, and defective HR repair. USP11 catalytic activity is required for proper recruitment of RAD51 and 53BP1 to repair foci. |
RNAi screen, siRNA knockdown, PARP inhibitor sensitivity assay, HR repair assay, immunofluorescence foci analysis |
The Journal of biological chemistry |
High |
20233726
|
| 2012 |
USP11 interacts with SMAD7 and deubiquitylates the type I TGFβ receptor ALK5, thereby stabilizing it and enhancing TGFβ-induced gene transcription. USP11 deubiquitylase activity is required to augment TGFβ signaling. RNAi depletion of USP11 inhibits TGFβ-induced SMAD2/3 phosphorylation, transcriptional responses, and epithelial-to-mesenchymal transition. |
Co-immunoprecipitation, in vitro/in vivo deubiquitylation assay, RNAi knockdown, reporter assay, SMAD2/3 phosphorylation assay, EMT assay |
Open biology |
High |
22773947
|
| 2013 |
Mitoxantrone was identified as an inhibitor of USP11 enzymatic activity via high-throughput biochemical screening of 2,000 FDA-approved compounds; mitoxantrone inhibits USP11 activity in vitro with IC50 < 10 nM for PDA cell survival. |
High-throughput enzymatic screening, in vitro USP11 activity assay, cell viability assay |
Molecular cancer research : MCR |
Medium |
23696131
|
| 2014 |
USP11 deubiquitinates and stabilizes PML protein, counteracting PML ubiquitin ligases RNF4 and KLHL20-Cul3-Roc1. In glioma, the Notch/Hey1 pathway transcriptionally represses USP11, leading to PML destabilization; Hey1 upregulation correlates with USP11 and PML downregulation and high-grade malignancy. |
RNAi screening, co-immunoprecipitation, in vivo/in vitro deubiquitination assay, knockdown/overexpression, orthotopic mouse model |
Nature communications |
High |
24487962
|
| 2014 |
USP11 forms a complex with p53, deubiquitinates p53, and stabilizes it; USP11 knockdown dramatically attenuates p53 induction in response to DNA damage stress. |
Co-immunoprecipitation, in vivo deubiquitination assay, siRNA knockdown, immunoblotting |
Journal of Zhejiang University. Science. B |
Medium |
25471832
|
| 2015 |
USP11 deubiquitylates γH2AX (but not canonical ubH2A-K119 or ubH2B-K120 in vitro); USP11 interacts with γH2AX both in vivo and in vitro. USP11 ablation enhances γH2AX ubiquitylation and causes misregulation and prolonged retention of 53BP1 and ubiquitin-conjugated proteins at DSB sites, with cellular hypersensitivity to γ-irradiation. |
Co-immunoprecipitation, in vitro/in vivo deubiquitylation assay, siRNA knockdown, immunofluorescence foci analysis, clonogenic survival assay |
The Journal of biological chemistry |
High |
26507658
|
| 2015 |
USP11 interacts with RNF4 (a SUMO-targeted ubiquitin E3 ligase) and deubiquitinates hybrid SUMO-ubiquitin chains to counteract RNF4 activity. USP11 stabilizes SUMO-enriched nuclear bodies, and in response to MMS-induced DNA damage, USP11 counteracts RNF4 to inhibit dissolution of nuclear bodies. |
Proteomic approach, co-immunoprecipitation, in vitro deubiquitination of SUMO-ubiquitin chains, immunofluorescence |
The Journal of biological chemistry |
Medium |
25969536
|
| 2015 |
USP11 deubiquitylates and stabilizes cIAP2 specifically (not cIAP1), protecting it from proteasomal degradation. High USP11 expression confers resistance to Smac mimetic-induced cIAP2 degradation and apoptosis; the TNFα/JNK pathway induces USP11 expression to maintain cIAP2 stability. |
Co-immunoprecipitation, in vitro/in vivo deubiquitylation assay, siRNA knockdown, apoptosis assay, xenograft model |
Cell death and differentiation |
High |
25613375
|
| 2016 |
USP11 interacts with XIAP (identified by protein complex purification coupled with mass spectrometry) and deubiquitylates it, stabilizing XIAP and thereby inhibiting anoikis and apoptosis to promote mammary tumorigenesis. Leu207 on the BIR2 domain of XIAP is required for interaction with USP11. |
DUB screen (transformation assay), protein complex purification + MS, co-immunoprecipitation, in vitro deubiquitylation assay, mutagenesis, anoikis/apoptosis assay, tumor colony formation assay |
EBioMedicine |
High |
28040451
|
| 2016 |
USP11 deubiquitinates and stabilizes VGLL4 protein; the USP domain of USP11 and the N-terminal region of VGLL4 are required for binding. USP11 knockdown promotes cell growth and migration in a YAP-dependent manner, suggesting USP11 acts as a tumor suppressor through the VGLL4/YAP-TEAD regulatory loop. |
Co-immunoprecipitation, in vivo deubiquitination assay, domain mapping, knockdown/overexpression, cell growth and migration assays |
American journal of cancer research |
Medium |
28042509
|
| 2016 |
USP11 deubiquitinates and stabilizes TβRII (TGF-β receptor type II), promoting TGFβ-1 signaling including SMAD2/3 phosphorylation and expression of fibronectin and smooth muscle actin; inhibition or knockdown of USP11 increases TβRII ubiquitination and reduces stability. |
Co-immunoprecipitation, in vitro/in vivo deubiquitination assay, siRNA knockdown, overexpression, immunoblotting |
Cell death & disease |
High |
27853171
|
| 2017 |
USP11 positively regulates nucleotide excision repair (NER) by deubiquitinating XPC and promoting its retention at UV-induced DNA damage sites. UV irradiation induces USP11 recruitment to chromatin and USP11 interaction with XPC in an XPC-ubiquitination-dependent manner. |
Co-immunoprecipitation, in vivo deubiquitination assay, chromatin fractionation, UV irradiation assay, NER functional assay |
Oncotarget |
Medium |
29228550
|
| 2018 |
USP11 deubiquitylates p21 in the nucleus, removing polyubiquitin chains and stabilizing p21 protein. USP11 reverses p21 polyubiquitylation mediated by SCF-SKP2, CRL4-CDT2, and APC/C-CDC20 in a cell-cycle-independent manner. Loss of USP11 causes p21 destabilization, inducing G1/S transition; DNA damage-induced p21 accumulation is abolished in USP11-depleted cells, abrogating the G2 checkpoint. |
Co-immunoprecipitation, in vivo and in vitro deubiquitylation assay, siRNA knockdown, cell cycle analysis, DNA damage assay, in vivo tumor model |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29666278
|
| 2018 |
FASN-induced PI3K-S6Kinase signaling phosphorylates USP11, enhancing its interaction with eIF4B. USP11 stabilizes eIF4B by deubiquitination, thereby promoting oncogenic protein translation in DLBCL. |
Biochemical co-immunoprecipitation, mass spectrometry, pharmacological and genetic inhibition, in vitro/in vivo deubiquitination assay, translation assay |
Nature communications |
High |
29483509
|
| 2018 |
USP11 deubiquitylates TβRII and stabilizes it in breast cancer cells, enhancing TGFβ downstream signaling and EMT. Modulating USP11 expression altered TβRII stability and breast cancer cell migratory capacity in vitro and metastasis in vivo. |
Co-immunoprecipitation, in vivo deubiquitination assay, siRNA/overexpression, migration assay, in vivo metastasis model |
Molecular cancer research : MCR |
Medium |
29724812
|
| 2018 |
USP11 deubiquitinates Snail and stabilizes it, promoting epithelial-to-mesenchymal transition in ovarian cancer cells. |
Co-immunoprecipitation, in vitro/in vivo deubiquitination assay, functional invasion/migration assay |
Oncology reports |
Medium |
30569152
|
| 2018 |
A crystal structure of USP11 in complex with a phage-display-identified peptide revealed a previously unknown binding site in USP11's noncatalytic UBL region that is absent in paralogs USP4 and USP15. This binding site modulates USP11's function in homologous recombination-mediated DNA repair as shown by reporter assays with a binding pocket-deficient double mutant. |
Phage display (NGPD), isothermal titration calorimetry, X-ray crystallography, reporter assay with mutagenesis |
The Journal of biological chemistry |
High |
30373771
|
| 2019 |
PTEN transcriptionally upregulates USP11 via the PI3K/FOXO pathway; USP11 in turn deubiquitinates and stabilizes PTEN, creating a feedforward regulatory loop. Mice lacking Usp11 display increased susceptibility to PTEN-dependent tumor initiation, growth, and metastasis. |
Co-immunoprecipitation, in vivo deubiquitination assay, knockout mouse model, tumor assays, FOXO pathway analysis |
Nature communications |
High |
30733438
|
| 2019 |
USP11 acts as a histone deubiquitinase that catalyzes H2AK119 and H2BK120 deubiquitination. USP11 physically associates with the NuRD chromatin remodeling complex; USP11-mediated histone deubiquitination and NuRD-associated histone deacetylation coordinate to allow timely termination of DNA repair and chromatin reorganization. |
Co-immunoprecipitation, in vitro/in vivo histone deubiquitination assay, chromatin condensation assay, DNA repair assay |
Nucleic acids research |
High |
31504778
|
| 2019 |
USP11 stabilizes PPP1CA by deubiquitinating and protecting it from proteasomal degradation; the USP11/PPP1CA complex promotes colorectal cancer progression by activating the ERK/MAPK signaling pathway. |
LC-MS/MS protein interaction identification, co-immunoprecipitation, in vivo deubiquitination assay, knockdown/overexpression, in vitro and in vivo tumor assays |
EBioMedicine |
Medium |
31521612
|
| 2020 |
USP11 deubiquitinates ARID1A and stabilizes it; the E3 ligase TRIM32 opposes USP11 by targeting ARID1A for degradation. USP11 depletion promotes ARID1A degradation and SCC development, while TRIM32 depletion inhibits SCC by stabilizing ARID1A. Syndecan-2 (SDC2) is identified as a downstream target of both ARID1A and USP11. |
Co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown, tumor proliferation/metastasis assays |
Cell reports |
Medium |
31914402
|
| 2020 |
USP11 interacts with NF90 and deubiquitinates it, stabilizing NF90 protein levels in HCC cells; USP11-promoted HCC proliferation and metastasis is dependent on NF90. |
Mass spectrometry, co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown, cell proliferation/metastasis assays |
American journal of cancer research |
Medium |
32509388
|
| 2020 |
CRL4-DCAF8 E3 ligase and USP11 oppositely regulate the stability of myeloid leukemia factors MLF1 and MLF2: DCAF8 promotes their degradation through ubiquitin-proteasome pathway while USP11 associates with MLF2 (and MLF1) and increases their stability. |
Co-immunoprecipitation, in vivo ubiquitination assay, immunoblotting |
Biochemical and biophysical research communications |
Low |
32703400
|
| 2021 |
USP11 deubiquitinates and stabilizes Beclin 1, promoting autophagy activation which in turn enhances ferroptosis after spinal cord ischemia-reperfusion injury. USP11 knockout reduces neuronal ferroptosis and improves functional recovery; autophagy inhibition weakens USP11-mediated ferroptosis. |
Co-immunoprecipitation, in vivo deubiquitination assay, USP11 KO mouse model, autophagy/ferroptosis functional assays, in vitro knockdown/overexpression |
Cell death and differentiation |
Medium |
34839355
|
| 2021 |
USP11 deubiquitinates and stabilizes NRF2; USP11 depletion suppresses cell proliferation and induces ferroptotic cell death due to ROS-mediated stress, effects that are largely abrogated by NRF2 overexpression. |
Co-immunoprecipitation, in vivo deubiquitination assay, siRNA knockdown, overexpression rescue, cell death/proliferation assays |
Oncogene |
Medium |
33531626
|
| 2021 |
USP11 deubiquitinates SPRTN metalloprotease by cleaving monoubiquitinated SPRTN in cells and in vitro. USP11 depletion impairs SPRTN deubiquitination, promotes SPRTN auto-proteolysis, causes accumulation of unrepaired DNA-protein cross-links, and hypersensitivity to DPC-inducing agents. |
Co-immunoprecipitation, in vitro deubiquitination assay, siRNA knockdown, DPC repair assay, formaldehyde sensitivity assay |
The Journal of biological chemistry |
High |
33567341
|
| 2021 |
USP11 deubiquitinates and stabilizes senataxin (SETX), preventing K48-ubiquitination and protein turnover. Loss of USP11 decreases SETX steady-state levels, reduces R-loop dissolution, and causes accumulation of R-loops and DNA double-strand breaks. Compensatory transcriptional downregulation of the E3 ubiquitin ligase KEAP1 partially restores SETX levels in USP11 KO cells. |
Co-immunoprecipitation, in vivo ubiquitination analysis, USP11 KO cells, R-loop immunofluorescence, DSB assay, KEAP1 overexpression |
Nature communications |
High |
34526504
|
| 2021 |
USP11 interacts with E2F1 and maintains E2F1 protein stability by removing its ubiquitin. E2F1 regulates USP11 expression at the transcriptional level, forming a positive feedback loop. This E2F1/USP11 axis promotes HCC proliferation, migration, and inhibits autophagy via ERK/mTOR pathway. |
Co-immunoprecipitation, in vivo ubiquitination assay, ChIP/promoter analysis, siRNA knockdown, functional cell assays |
Cancer letters |
Medium |
34044068
|
| 2021 |
USP11 deubiquitinates KLF4 by removing K63-dependent polyubiquitination from it, thereby destabilizing KLF4 expression. USP11 depletion inhibits HCC cell growth and chemoresistance by enhancing KLF4 stability. |
Proteomic approach (IP/MS), co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown, cell growth assays |
Journal of cellular and molecular medicine |
Medium |
34114341
|
| 2021 |
USP11 restricts autophagy: USP11 KO in mammalian cells results in elevated autophagic flux. USP11 coprecipitates with autophagy-specific class III PI3K complex I and limits its interaction with NRBF2, decreasing lipid kinase activity and recruitment of WIPI proteins. USP11 also interacts with and stabilizes mTOR kinase. USP11 homolog depletion in C. elegans triggers hyperactivation of autophagy and protects against amyloid-β aggregation-induced paralysis. |
Co-immunoprecipitation, KO cell analysis, autophagic flux assay, PI3K activity assay, C. elegans genetic model |
The Journal of biological chemistry |
High |
34600886
|
| 2021 |
USP11 deubiquitinates RAE1, and USP11 is associated with the mitotic spindle. USP11 knockdown leads to multipolar spindle formation and drastically reduces cell proliferation; USP11 controls RAE1 ubiquitination at the mitotic spindle, modulating its interaction with NuMA. |
Co-immunoprecipitation, in vivo ubiquitination assay, lentiviral knockdown, immunofluorescence (spindle localization), flow cytometry |
PloS one |
Medium |
29293652
|
| 2021 |
Mouse Usp11 stabilizes the transcription factor Sox11 via deubiquitination in the developing cerebral cortex. Usp11 deficiency impairs layer 6 neuron production, delays late-born neuronal migration, and disturbs cognition and anxiety behaviors. A disease-associated Usp11 mutant fails to stabilize Sox11 and is unable to support cortical neurogenesis and neuronal migration. |
Usp11 knockout mouse, in vivo ubiquitination assay, immunoblotting, behavioral testing, cortical layer analysis, mutant rescue experiments |
Science advances |
High |
33579706
|
| 2021 |
USP11 stabilizes p53 by deubiquitination and p53 transcriptionally represses KLF2, thereby activating the NF-κB pathway and promoting neuroinflammation after intracerebral hemorrhage. USP11 silencing blocks pro-inflammatory cytokine release by downregulating p53, protecting against neurological impairment. |
siRNA knockdown, co-immunoprecipitation, in vivo deubiquitination assay, ChIP (p53 binding to KLF2 promoter), in vivo rat ICH model |
Molecular therapy. Methods & clinical development |
Medium |
34141823
|
| 2022 |
USP11 interacts with and deubiquitinates Sirt3, stabilizing it and thereby reducing oxidative stress-induced ferroptosis. USP11 knockout exacerbates intervertebral disc degeneration and is reversed by Sirt3 overexpression. |
IP/MS, co-immunoprecipitation, in vivo deubiquitination assay, Sirt3 KO mouse, USP11 KO mouse, rescue experiments |
Redox biology |
High |
37099926
|
| 2022 |
ERK1/2 phosphorylates USP11 at Ser905, which promotes cytoplasmic localization of USP11. In the cytoplasm, USP11 colocalizes and interacts with p21, catalyzing removal of polyubiquitin chains from cytoplasmic p21 and stabilizing it. USP11-mediated stabilization of cytoplasmic p21 induces breast cancer cell proliferation. |
Phosphorylation mapping, co-immunoprecipitation, subcellular fractionation, in vitro/in vivo deubiquitination assay, knockdown/overexpression, cell proliferation assay |
International journal of biological sciences |
Medium |
35414784
|
| 2022 |
Non-mitochondrial HK2 directly interacts with CD133 and promotes binding of USP11 to CD133, thereby inhibiting CD133 polyubiquitylation and degradation. USP11-mediated deubiquitination of CD133 enhances cancer stem cell stemness and tumor growth. |
Co-immunoprecipitation, mass spectrometry, in vitro/in vivo ubiquitination assay, immunofluorescence, flow cytometry |
Cancer communications |
Medium |
35975322
|
| 2023 |
USP11 interacts with LSH chromatin-remodeling protein and stabilizes it via deubiquitination; erastin treatment disrupts USP11-LSH interaction, increasing LSH ubiquitination and degradation. LSH binds the CYP24A1 promoter to promote its transcription, which inhibits ferroptosis in colorectal cancer cells. |
Co-immunoprecipitation, in vivo deubiquitination assay, ChIP analysis, siRNA knockdown, ferroptosis assay |
Cell death & disease |
Medium |
37414755
|
| 2023 |
USP11 interacts with eEF1A1 and deubiquitinates it on Lys439, preventing ubiquitin-mediated degradation. Elevated eEF1A1 binds SP1, driving SP1-dependent HGF gene transcription and PI3K/AKT activation, promoting EMT and metastasis in HCC. |
Co-immunoprecipitation, in vivo deubiquitination assay with site-specific K439 mutant, ChIP, knockdown/overexpression, functional EMT/metastasis assays |
Oncogene |
Medium |
37973952
|
| 2023 |
USP11 stabilizes SMYD5 (a lysine methyltransferase) post-transcriptionally in the context of HIV-1 transcription; the Tat cofactor function of USP11 is required for SMYD5 protein level increases in cells expressing Tat. SMYD5 methylates Tat in vitro. |
siRNA knockdown, immunoblotting, in vitro methylation assay, co-immunoprecipitation |
Cell reports |
Low |
36897778
|
| 2024 |
USP11 deubiquitinates both AR (androgen receptor) and c-Myc to increase their protein stability, and also deubiquitinates H2A-K119Ub (a repressive histone mark) on promoters of AR and c-Myc genes to increase their transcription. ChIP-seq with catalytic-inactive USP11 mutant confirmed both mechanisms. |
RNA-seq, ChIP-seq, catalytic-inactive mutant, co-immunoprecipitation, in vivo deubiquitination assay, knockdown/rescue, cell growth assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
39052835
|
| 2024 |
USP11 deubiquitinates and stabilizes DNMT3A, opposing degradation by CUL4-DCAF8 E3 ligase. USP11 also enhances DNMT3A SUMOylation by promoting DNMT3A interaction with SUMO E3 ligases, and enhances DNMT3A binding to the polycomb complex and maintains its DNA methyltransferase activity. |
Co-immunoprecipitation, in vivo ubiquitination/SUMOylation assays, USP11 stable expression rescue, E1 enzyme inhibition, immunoprecipitation with SUMO E3 ligases, MTase activity assay |
bioRxiv (preprint)preprint |
Medium |
40161590
|
| 2024 |
USP11 deubiquitinates E-cadherin at K738, stabilizing it. USP11 binds E-cadherin through its C-terminal region. This deubiquitinase activity of USP11 maintains luminal differentiation of mammary epithelial cells and suppresses luminal breast cancer; deubiquitinase-inactive USP11 mutant fails to support these functions. |
USP11 knockout mice, catalytic-inactive mutant, in vivo deubiquitination assay, site-specific K738 mutagenesis, co-immunoprecipitation, domain mapping |
The Journal of biological chemistry |
High |
39270819
|
| 2024 |
USP11 depletion leads to increased MDM2 polyubiquitination and reduced MDM2 half-life, elevating p53 protein levels and p21 mRNA in a p53-dependent manner. USP11 acts as a deubiquitinase for MDM2, thereby regulating the MDM2-p53-p21 axis and cell cycle progression. USP11 depletion also promotes cellular senescence in a deubiquitinase-activity-dependent manner. |
siRNA knockdown, polyubiquitination assay, protein half-life analysis, immunoblotting, cell cycle analysis, senescence assay |
Biochemical and biophysical research communications |
Medium |
38901057
|
| 2024 |
USP11 deubiquitinates TPIT transcription factor and stabilizes it in functioning ACTH pituitary tumors, thereby enhancing POMC transcription and ACTH secretion. USP11 knockdown reduces both POMC transcription and ACTH secretion in vitro and in vivo. |
Co-immunoprecipitation, in vivo deubiquitination assay, siRNA knockdown, in vivo model, POMC/ACTH secretion assay |
Acta neuropathologica communications |
Medium |
39910602
|
| 2024 |
USP11 promotes angiogenesis by binding PRDX2 and removing its K63-linked polyubiquitination, facilitating PRDX2 nuclear translocation. Nuclear PRDX2 promotes concurrent nuclear translocation of c-MYC, which enhances transcription of KDR (VEGFR2) and activates VEGFR2 signaling. USP11 KO markedly inhibits angiogenesis in vivo and in vitro. |
Co-immunoprecipitation, in vivo deubiquitination assay (K63-linkage specificity), USP11 KO mouse model, retinal angiogenesis model, nuclear fractionation, reporter assay |
Angiogenesis |
Medium |
40199774
|
| 2025 |
The UBL2 domain of USP11 directs its selectivity toward K48-linked polyubiquitin chains; removal of UBL2-IDR reduces ability to cleave K48 chains most significantly. This K48 chain selectivity function of UBL2 is not shared by paralogs USP4 and USP15. FDA-approved drugs Fenoldopam and Olanzapine were identified as selective USP11 inhibitors that act through a unique scaffold. |
In vitro Ub-tetramer cleavage assay, cell-based K48-ubiquitin analysis, UBL2 domain deletion/mutation, paralog comparison, AI-based virtual screening, in vitro and cell-based inhibitor assays |
The Journal of biological chemistry |
High |
41207628
|
| 2025 |
RRM1 interacts with USP11 in the cytoplasm; ionizing radiation-induced recruitment of RRM1 to LaminB1 facilitates USP11 binding to the nuclear pore complex and nuclear translocation of USP11. In the nucleus, USP11 binds E2F1 and prevents ubiquitin-mediated E2F1 degradation, enhancing transcription of RAD51AP1 to promote homologous recombination. |
Co-immunoprecipitation, nuclear fractionation, NPC binding assay, in vivo ubiquitination assay, ChIP, dominant-negative RRM1 mutant, HR repair assay |
Cell death discovery |
Medium |
39695160
|
| 2025 |
SPRYD3-MYCBP2 E3 ligase complex promotes ubiquitination of USP11 specifically at cysteine 318 (non-canonical ubiquitination), which promotes bipolar spindle formation and mitotic slippage in the presence of microtubule targeting drugs. |
Co-immunoprecipitation, ubiquitination site mapping (C318), site-directed mutagenesis, mitotic spindle assay, mitotic slippage assay |
The Journal of biological chemistry |
Medium |
41052634
|
| 2025 |
USP11 deubiquitinates and stabilizes HINT3, and HINT3 interacts with BCL2. USP11 overexpression increases BCL2 levels, and HINT3 knockdown depletes BCL2, suggesting USP11 promotes endothelial apoptosis resistance in pulmonary arterial hypertension through HINT3-BCL2. |
Co-immunoprecipitation, in vivo ubiquitination/degradation assay, knockdown/overexpression, immunoblotting |
Journal of respiratory biology and translational medicine |
Low |
40376595
|
| 2025 |
USP11 interacts with and deubiquitinates GSK3β, modulating its Ser9 phosphorylation level and enzymatic activity, thereby impairing synaptic integrity in the prefrontal cortex under chronic stress. USP11 deficiency protects against stress-induced synaptic injury and depression-like behaviors via GSK3β/mTOR signaling. |
IP-MS, co-immunoprecipitation, in vivo deubiquitination assay, phosphorylation analysis, USP11 KO mouse, behavioral testing |
Neurobiology of stress |
Medium |
41889422
|
| 2025 |
USP11 interacts with and deubiquitinates PGAM5, stabilizing it in neurotoxic astrocytes after intracerebral hemorrhage. PGAM5 promotes mPTP opening and Drp1-mediated mitochondrial fission, amplifying mtDNA leakage and cGAS-STING pathway activation. Astrocyte-specific Usp11 KO suppresses neurotoxic astrocyte reactivity and improves neurological recovery. |
Co-immunoprecipitation, in vivo ubiquitination assay, astrocyte-specific KO mouse, mitochondrial function assay, mtDNA quantification, cGAS-STING pathway analysis |
Advanced science |
Medium |
41201111
|
| 2025 |
Usp11 maintains survival of marginal zone B cells by regulating ubiquitination of Notch ligands DLL1 and JAG2; Usp11-/- mice show higher MZ B cell survival rates after total body irradiation. |
Co-IP, ubiquitination assay, Usp11-/- mouse model, flow cytometry, single-cell sequencing, histological analysis |
Cell death & disease |
Medium |
39904982
|
| 2025 |
USP11 deubiquitinates OTUD5, and this mechanism implicates the OTUD5-STING signaling pathway in the inflammatory response of endothelial cells after radiation. USP11 KO mice show decreased radiation-induced pneumonitis with reduced proinflammatory cytokines. |
Comprehensive proteome and ubiquitinome analysis, co-immunoprecipitation, Western blot, Usp11-/- mouse model, cytokine measurement |
International journal of radiation oncology, biology, physics |
Medium |
38364946
|
| 2025 |
USP11 stabilizes SFTPC (surfactant protein C) by interacting with, deubiquitinating it, and extending its half-life; USP11 stabilizes mutant SFTPC-I73T significantly more than wild-type. USP11 depletion in hiPSC-derived alveolar organoids mitigates SFTPC-I73T-induced fibrosis. |
CRISPR/Cas9 screen, immunoprecipitation, TUBEs assay for ubiquitination, hiPSC-derived alveolar organoids, bleomycin mouse model |
Theranostics |
Medium |
40225577
|
| 2025 |
USP11 stabilizes EGFR and TRAF6 by removing K48-linked ubiquitin chains, preventing their proteasomal degradation; this potentiates both EGFR and Toll-like receptor signaling in colorectal cancer cells. |
Co-immunoprecipitation, in vivo K48-ubiquitination assay, USP11 KO and overexpression cell lines, xenograft model, mitoxantrone inhibition |
Cell death & disease |
Medium |
41419456
|
| 2025 |
USP11 deubiquitinates CK2α, stabilizing its protein level and promoting mitochondrial dysfunction. USP11 KO in mouse prefrontal cortex protects against stress-induced synaptic injury and depressive-like behaviors, effects reversed by CK2α stabilization. |
IP-MS, co-immunoprecipitation, in vivo deubiquitination assay, USP11 KO mouse, CK2α inhibitor (CX4945), primary neuronal cultures |
CNS neuroscience & therapeutics |
Medium |
42231570
|