| 2002 |
USP11 was identified as a RanBPM-binding protein via yeast two-hybrid; USP11 interacts with RanBPM in vivo (co-IP), deubiquitinates RanBPM in vitro (recombinant USP11 inhibited ubiquitin conjugation to RanBPM in a dose-dependent manner), and stabilizes RanBPM against proteasomal degradation. USP11 localizes primarily to the nucleus in non-dividing cells. |
Yeast two-hybrid, co-immunoprecipitation, in vitro deubiquitination assay, pulse-chase analysis with proteasome inhibitors, immunofluorescence |
The Biochemical journal |
High |
12084015
|
| 2004 |
USP11 forms specific complexes with BRCA2 (immunopurification-MS and Co-IP) and can deubiquitinate BRCA2 in transient overexpression assays; a catalytically inactive USP11 mutant had no effect on BRCA2 ubiquitination or protein levels. USP11 participates in DNA damage repair functions within the BRCA2 pathway, and antagonism of USP11 (dominant-negative mutant or RNAi) increased cellular sensitivity to mitomycin C in a BRCA2-dependent manner. |
Immunopurification-mass spectrometry, Co-IP, transient overexpression deubiquitination assay, catalytic-dead mutant, RNAi, cell survival assay |
Molecular and cellular biology |
High |
15314155
|
| 2007 |
USP11 specifically regulates IKKα expression at the transcriptional level. Knockdown of USP11 dramatically enhances NF-κB activity in response to TNFα, and depletion of USP11 or IKKα abrogates p53 induction upon TNFα exposure. Ectopic IKKα expression in USP11-silenced cells restores p53 expression, placing USP11 upstream of an IKKα-p53 signaling pathway. |
RNAi knockdown, ectopic expression rescue, reporter assays, western blotting |
The Journal of biological chemistry |
Medium |
17897950
|
| 2008 |
USP11 interacts with HPV-16 E7 (yeast two-hybrid and co-IP), deubiquitinates E7, and stabilizes E7 protein by reducing ubiquitination and attenuating degradation. A catalytically inactive USP11 mutant abolished deubiquitinating ability and returned E7 to normal degradation rates. USP11 also modulates E7 biological function and its contribution to cell transformation. |
Yeast two-hybrid, Co-IP, ubiquitination assay, catalytic-dead mutant, steady-state protein level analysis |
The Journal of biological chemistry |
High |
18408009
|
| 2010 |
USP11 was identified as an IκBα-associated deubiquitinase (proteomic approach). Recombinant USP11 catalyzes deubiquitination of IκBα in vitro; USP11 overexpression inhibits IκBα ubiquitination; USP11 knockdown enhances TNFα-induced IκBα ubiquitination and NF-κB activation. A catalytically inactive USP11 mutant partially inhibits TNFα- and IKKβ-induced NF-κB activation, indicating a non-catalytic function as well. |
Proteomic/Co-IP identification, in vitro deubiquitination assay with recombinant protein, RNAi knockdown, catalytic-dead mutant, NF-κB reporter assay |
Cellular signalling |
High |
19874889
|
| 2010 |
RNAi screen identified USP11 as required for homologous recombination (HR) repair of DNA double-strand breaks. Silencing USP11 causes spontaneous DDR activation, hypersensitivity to PARP inhibition and ionizing radiation, defective HR, and misregulation of RAD51 and 53BP1 recruitment to repair foci in a manner dependent on USP11 catalytic activity. |
RNAi screen (synthetic lethality with PARP inhibitor AZD2281), siRNA knockdown, HR repair assay, immunofluorescence foci analysis |
The Journal of biological chemistry |
High |
20233726
|
| 2012 |
USP11 interacts with SMAD7 and with the type I TGFβ receptor ALK5. USP11 deubiquitylates ALK5, resulting in enhanced TGFβ-induced gene transcription. RNAi depletion of USP11 inhibits TGFβ-induced SMAD2/3 phosphorylation, TGFβ-mediated transcriptional responses, and TGFβ-induced epithelial-to-mesenchymal transition. The deubiquitylase activity of USP11 is required for these effects. |
Co-IP, ubiquitination assay, RNAi knockdown, phospho-SMAD2/3 western blot, transcription reporter assay, EMT assay |
Open biology |
High |
22773947
|
| 2013 |
High-throughput biochemical screen of 2,000 FDA-approved compounds identified mitoxantrone as an inhibitor of USP11 enzymatic activity. Mitoxantrone impacts pancreatic cancer cell survival with IC50 <10 nM and shows 40- to 20,000-fold greater potency than gemcitabine across PDA cell lines; USP11 silencing also enhanced gemcitabine sensitivity. |
High-throughput enzymatic inhibition screen, in vitro drug sensitivity assay, RNAi knockdown |
Molecular cancer research : MCR |
Medium |
23696131
|
| 2014 |
USP11 deubiquitinates and stabilizes PML, counteracting PML ubiquitin ligases RNF4 and KLHL20-Cul3-Roc1. USP11 was identified by RNAi screening; its expression is transcriptionally repressed by Notch/Hey1, leading to PML destabilization. Notch/Hey1-induced downregulation of USP11/PML confers malignant characteristics including proliferation, invasiveness, and therapeutic resistance in glioma. |
RNAi screen, Co-IP, ubiquitination assay, loss-of-function with cellular phenotype readouts (proliferation, invasion, tumor growth in orthotopic mouse model) |
Nature communications |
High |
24487962
|
| 2014 |
USP11 forms specific complexes with p53 (co-IP) and stabilizes p53 by deubiquitinating it. Downregulation of USP11 dramatically attenuates p53 induction in response to DNA damage stress. |
Co-immunoprecipitation, ubiquitination assay, RNAi knockdown |
Journal of Zhejiang University. Science. B |
Medium |
25471832
|
| 2015 |
USP11 specifically and selectively deubiquitylates cIAP2 to stabilize it, leading to resistance to Smac mimetics. USP11 overexpression is found in colorectal cancer and melanoma; the TNFα/JNK pathway induces USP11 expression, which maintains cIAP2 stability as an alternative TNFα-dependent cell survival pathway. |
Co-IP, ubiquitination assay, RNAi knockdown, apoptosis assay, xenograft model |
Cell death and differentiation |
High |
25613375
|
| 2015 |
USP11 is a negative regulator of γH2AX ubiquitylation by RNF8/RNF168. USP11 deubiquitylates γH2AX both in vivo and in vitro but not canonical H2A-K119ub or H2B-K120ub in vitro. USP11 ablation enhances γH2AX ubiquitylation and causes prolonged retention of 53BP1 and ubiquitin-conjugated proteins at DSB sites, and USP11-depleted cells are hypersensitive to γ-irradiation. |
In vivo and in vitro deubiquitylation assays, Co-IP, siRNA knockdown, immunofluorescence foci, irradiation sensitivity assay |
The Journal of biological chemistry |
High |
26507658
|
| 2015 |
USP11 was identified as a functional interactor of RNF4 (proteomic approach) and can deubiquitinate hybrid SUMO-ubiquitin chains to counteract RNF4. USP11 stabilizes SUMO-enriched nuclear bodies and counteracts RNF4-mediated dissolution of nuclear bodies in response to DNA damage (methyl methanesulfonate). |
Proteomic identification, in vitro deubiquitination of hybrid SUMO-ubiquitin chains, cell-based nuclear body analysis, DNA damage response assay |
The Journal of biological chemistry |
Medium |
25969536
|
| 2016 |
USP11 was identified as a mammary tumor-promoting DUB by an unbiased transformation screen. XIAP was identified as a USP11 substrate by protein complex purification/MS; USP11 deubiquitylates XIAP to stabilize it, inhibiting cell anoikis and apoptosis and promoting tumorigenesis. Molecular modeling and mutagenesis revealed Leu207 on the BIR2 domain of XIAP facilitates its interaction with USP11. |
DUB transformation screen, protein complex purification/MS, Co-IP, ubiquitination assay, molecular modeling + mutagenesis, cell transformation assay, apoptosis assay, IHC |
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 mutual binding. USP11 knockdown promotes cell growth, migration, and invasion in a YAP-dependent manner. |
Co-IP, in vitro/in vivo ubiquitination assay, RNAi knockdown, domain-mapping experiments, cell functional assays |
American journal of cancer research |
Medium |
28042509
|
| 2016 |
USP11 promotes TGFβ-1 signaling through deubiquitination and stabilization of TβRII (TGFβ receptor type II). Inhibition or downregulation of USP11 increases TβRII ubiquitination and reduces its stability, attenuating SMAD2/3 phosphorylation and downstream targets fibronectin and smooth muscle actin. |
Co-IP, ubiquitination assay, RNAi knockdown, phospho-SMAD2/3 western blot, USP11 overexpression, in vivo mouse model |
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-IP, ubiquitination assay, chromatin fractionation, UV irradiation NER assay, RNAi knockdown |
Oncotarget |
Medium |
29228550
|
| 2018 |
USP11 was identified as a deubiquitylase that binds p21 in the nucleus, catalyzes removal of polyubiquitin chains conjugated onto p21, and stabilizes p21 protein. USP11 reverses p21 polyubiquitylation mediated by SCFSKP2, CRL4CDT2, and APC/CCDC20 in a cell-cycle-independent manner. Loss of USP11 destabilizes p21, induces G1/S transition, abolishes p21 accumulation after DNA damage, abrogates the G2 checkpoint, and induces apoptosis. USP11-mediated p21 stabilization inhibits cell proliferation and tumorigenesis in vivo. |
Co-IP, ubiquitination assay, protein half-life analysis, cell cycle analysis, DNA damage response assay, RNAi + rescue, in vivo tumor assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
29666278
|
| 2018 |
USP11 forms a complex with eIF4B and deubiquitinates it, stabilizing eIF4B and enhancing its activity. FASN-induced PI3K-S6Kinase signaling phosphorylates USP11, enhancing its interaction with eIF4B and promoting oncogenic translation in DLBCL. |
Co-IP, mass spectrometry, ubiquitination assay, pharmacological and genetic approaches (kinase inhibitors, RNAi), protein translation assay |
Nature communications |
High |
29483509
|
| 2018 |
USP11 enhances TGFβ-induced EMT and self-renewal in breast cancer by deubiquitinating and stabilizing TGFβ receptor type II (TGFBR2). USP11 modulation altered TGFβ downstream signaling and metastasis in vivo. |
USP11 overexpression/knockdown, TGFBR2 ubiquitination assay, Co-IP, TGFβ signaling assays, in vivo metastasis model |
Molecular cancer research : MCR |
Medium |
29724812
|
| 2018 |
USP11 deubiquitinates RAE1 at the mitotic spindle and functionally modulates RAE1's interaction with NuMA. USP11 knockdown drastically reduces cell proliferation and increases multipolar spindle formation; USP11 is associated with the mitotic spindle and does not regulate spindle assembly checkpoint inactivation. |
Lentiviral knockdown, ubiquitination assay, co-IP, immunofluorescence (spindle localization), cell proliferation assay, spindle morphology analysis |
PloS one |
Medium |
29293652
|
| 2018 |
A phage display/next-generation sequencing strategy discovered unique peptide-binding sites in USP11's noncatalytic UBL domain. Crystal structure of a USP11-peptide complex revealed a previously unknown binding site absent in paralogs USP4 and USP15. A binding-pocket-deficient double mutant showed this site modulates USP11's function in homologous recombination-mediated DNA repair. |
Phage display, next-generation sequencing, isothermal titration calorimetry, X-ray crystallography, HR reporter assay, mutagenesis |
The Journal of biological chemistry |
High |
30373771
|
| 2019 |
USP11 stabilizes PPP1CA by deubiquitinating it and protecting it from proteasome-mediated degradation. The USP11/PPP1CA complex promotes colorectal cancer progression by activating the ERK/MAPK signaling pathway. |
LC-MS/MS (protein interaction identification), Co-IP, ubiquitination assay, in vitro and in vivo tumor growth assays, ERK/MAPK signaling readout |
EBioMedicine |
Medium |
31521612
|
| 2019 |
USP11 acts as a histone deubiquitinase that catalyzes H2AK119 and H2BK120 deubiquitination. USP11 is physically associated 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, involving chromatin condensation and genomic stability. |
Co-IP, in vitro histone deubiquitination assay, chromatin fractionation, DNA repair assay, cell survival assay |
Nucleic acids research |
High |
31504778
|
| 2019 |
PTEN transcriptionally upregulates USP11 via the PI3K/FOXO pathway. USP11 in turn deubiquitinates and stabilizes PTEN, forming a feedforward regulatory loop. Mice lacking Usp11 display increased susceptibility to PTEN-dependent tumor initiation, growth, and metastasis. |
Transcriptional reporter assays, Co-IP, ubiquitination assay, Usp11 knockout mice, tumor initiation/growth/metastasis assays |
Nature communications |
High |
30733438
|
| 2020 |
TRIM32 (E3 ligase) and USP11 (deubiquitinase) antagonistically control ARID1A protein stability. USP11 depletion promotes ARID1A degradation and SCC development; TRIM32 depletion stabilizes ARID1A and inhibits SCC. SDC2 was identified as a downstream target of the ARID1A/USP11 axis. |
Co-IP, ubiquitination assay, RNAi knockdown/overexpression, cell proliferation/metastasis/chemoresistance assays, epistasis by rescue experiments |
Cell reports |
Medium |
31914402
|
| 2020 |
RNAi screen of all DUBs in breast cancer cells identified USP11 as a regulator of ERα transcriptional activity. Mass spectrometry revealed changes in proteome and ubiquitinome upon USP11 knockdown in the presence of estradiol. USP11 expression is induced by estradiol (blocked by tamoxifen) in ERα-positive cells. |
RNAi functional screen, mass spectrometry (proteome/ubiquitinome), RNA sequencing, ERα target gene reporter assays |
Cancer research |
Medium |
33004351
|
| 2021 |
USP11 promotes autophagy activation by stabilizing Beclin 1 via deubiquitination, which leads to autophagy-dependent ferroptosis after spinal cord ischemia-reperfusion injury. USP11 knockdown in vitro and knockout in vivo decreased neuronal ferroptosis; autophagy inhibition weakened USP11-mediated ferroptosis. |
Co-IP, ubiquitination assay, siRNA knockdown, USP11 KO mouse model, autophagic flux assay, ferroptosis assays (lipid peroxidation markers), functional recovery assay |
Cell death and differentiation |
High |
34839355
|
| 2021 |
USP11 deubiquitinates NRF2, stabilizing it and protecting it from proteasome-mediated degradation. USP11 depletion leads to suppression of cell proliferation and induction of ferroptotic cell death via ROS-mediated stress, which is largely abrogated by NRF2 overexpression. |
Co-IP, ubiquitination assay, RNAi knockdown, NRF2 overexpression rescue, ferroptosis assay (ROS measurement), cell proliferation assay |
Oncogene |
High |
33531626
|
| 2021 |
USP11 interacts with and deubiquitinates E2F1 to maintain E2F1 protein stability. E2F1 in turn regulates USP11 expression at the transcriptional level, forming a positive E2F1/USP11 feedback loop that promotes HCC cell proliferation, migration, and inhibits autophagy via ERK/mTOR pathway. |
Co-IP, ubiquitination assay, transcription assay, RNAi + rescue, in vitro and in vivo tumor assays, ERK/mTOR signaling readout |
Cancer letters |
Medium |
34044068
|
| 2021 |
USP11 deubiquitinates SPRTN metalloprotease, cleaving monoubiquitinated SPRTN in cells and in vitro. USP11 interacts with SPRTN; USP11 depletion impairs SPRTN deubiquitination, promotes SPRTN auto-proteolysis in response to formaldehyde-induced DNA-protein crosslinks (DPCs), and causes accumulation of unrepaired DPCs and hypersensitivity to DPC-inducing agents. |
Co-IP, in vitro deubiquitination assay, DPC repair assay, DPC accumulation measurement, cell sensitivity assay |
The Journal of biological chemistry |
High |
33567341
|
| 2021 |
USP11 deubiquitinates senataxin (SETX) — USP11 depletion increases SETX K48-ubiquitination and protein turnover, decreasing steady-state SETX levels and reducing R-loop dissolution. Loss of USP11 reduces SETX enrichment at the KEAP1 promoter, leading to R-loop accumulation and formation of double-strand breaks. KEAP1 opposes USP11 by promoting SETX K48-ubiquitination and degradation. |
Co-IP, ubiquitination assay (K48-specific), USP11 KO cells, R-loop immunofluorescence/slot blot, SETX ChIP, DSB assay, KEAP1 overexpression |
Nature communications |
High |
34526504
|
| 2021 |
USP11 coprecipitates with the autophagy-specific class III phosphatidylinositol 3-kinase complex I (PI3KC3-C1) and limits its interaction with nuclear receptor-binding factor 2 (NRBF2), decreasing lipid kinase activity and reducing recruitment of WIPI proteins to the autophagosomal membrane. USP11 also stabilizes mTOR, further restraining autophagy induction. USP11 KO elevates autophagic flux. |
Co-IP, lipid kinase activity assay, WIPI2 puncta analysis, autophagic flux assay (USP11 KO mammalian cells), C. elegans depletion + amyloid-β protection assay, mTOR stability assay |
The Journal of biological chemistry |
High |
34600886
|
| 2021 |
Usp11 stabilizes Sox11 protein via deubiquitination in embryonic cerebral cortex. Usp11 deficiency impairs cortical layer 6 neuron production and delays late-born neuronal migration; the disease-associated Usp11 mutant fails to stabilize Sox11. These functions are required for proper cortical neurogenesis and cognition. |
Usp11 KO mouse, Co-IP, ubiquitination assay, cortical layer analysis, behavioral assays, disease-associated mutant characterization |
Science advances |
High |
33579706
|
| 2021 |
USP11 deubiquitinates NF90 (nuclear factor 90), protecting it from proteasomal degradation by removing polyubiquitin chains. USP11 and NONO colocalize and interact in the nucleus of melanoma cells; USP11 knockdown decreases NONO levels and inhibits melanoma cell proliferation, which is rescued by NONO overexpression. |
Co-localization (immunofluorescence), Co-IP, ubiquitination assay, RNAi knockdown + rescue, proliferation assay |
Journal of cellular and molecular medicine |
Medium |
33369124
|
| 2022 |
Non-mitochondrial HK2 directly interacts with CD133 and promotes recruitment of USP11 to CD133, thereby inhibiting CD133 polyubiquitylation and degradation. USP11 stabilizes CD133 by removing ubiquitin chains, enhancing cancer cell stemness and tumor growth in SCLC. |
Co-IP, mass spectrometry, in vitro and in vivo ubiquitination assay, flow cytometry, xenograft model, immunofluorescence |
Cancer communications |
Medium |
35975322
|
| 2022 |
ERK1/2 phosphorylates USP11 at Ser905, promoting cytoplasmic localization of USP11. In the cytoplasm, USP11 colocalizes with and deubiquitinates cytoplasmic p21, stabilizing it and promoting breast cancer cell proliferation in vitro and in vivo. |
Co-IP, ubiquitination assay, phosphosite mapping (Ser905), ERK1/2 kinase assay, subcellular fractionation, in vitro and in vivo proliferation assays |
International journal of biological sciences |
Medium |
35414784
|
| 2023 |
USP11 interacts with and deubiquitinates Sirt3 (IP/MS and Co-IP), stabilizing it to reduce oxidative stress-induced ferroptosis. USP11 KO mice exhibit exacerbated intervertebral disc degeneration that is reversed by Sirt3 overexpression, establishing USP11 upstream of Sirt3 in ferroptosis regulation. |
IP/MS, Co-IP, ubiquitination assay, USP11 KO and Sirt3 KO mice, ferroptosis assay (GPX4, GSH), in vivo rescue experiment, pain behavioral scores |
Redox biology |
High |
37099926
|
| 2023 |
USP11 interacts with and deubiquitinates eEF1A1 at Lys439, inhibiting its ubiquitin-mediated degradation. Elevated eEF1A1 binds SP1, driving SP1 binding to the HGF gene promoter to increase HGF transcription, activating downstream PI3K/AKT signaling and promoting EMT and metastasis in HCC. |
Co-IP, ubiquitination assay (site-specific K439 mapping), ChIP assay (SP1 on HGF promoter), PI3K/AKT signaling readout, in vitro and in vivo metastasis assays |
Oncogene |
Medium |
37973952
|
| 2023 |
USP11 interacts with and stabilizes LSH (lymphoid-specific helicase) by deubiquitination; this interaction is disrupted by erastin treatment. LSH in turn activates transcription of CYP24A1 by binding its promoter and reducing H3K27me3, inhibiting excessive Ca2+ influx and lipid peroxidation to confer ferroptosis resistance in colorectal cancer. |
Co-IP, ubiquitination assay, ChIP (LSH on CYP24A1 promoter), H3K27me3 analysis, Ca2+ influx assay, lipid peroxidation assay, ferroptosis assay |
Cell death & disease |
Medium |
37414755
|
| 2023 |
USP11 promotes SMYD5 protein stabilization in HIV-infected T cells. USP11 is required to elevate SMYD5 protein levels when Tat is expressed; loss of USP11 prevents Tat-induced SMYD5 upregulation. SMYD5 methylates Tat in vitro and activates the HIV-1 promoter. |
Knockdown of USP11, western blotting for SMYD5, in vitro methylation assay (SMYD5 on Tat), HIV-1 transcription assay |
Cell reports |
Medium |
36897778
|
| 2024 |
USP11 deubiquitinates AR and c-Myc proteins to increase their stability, and also deubiquitinates the repressive histone mark H2A-K119Ub on promoters of AR and c-Myc genes to increase their transcription. Catalytic-inactive USP11 mutant significantly decreased chromatin binding by AR and c-Myc (ChIP-seq). USP11 KD significantly inhibited PCa cell growth. |
RNAi knockdown, catalytic-dead mutant replacement, RNA-seq, ChIP-seq, ubiquitination assay, Co-IP, rescue with AR/c-Myc re-expression |
Proceedings of the National Academy of Sciences of the United States of America |
High |
39052835
|
| 2024 |
USP11 deubiquitinates E-cadherin at K738 and maintains luminal differentiation and DNA damage repair in mammary epithelial cells. Usp11 KO mice show reduced E-cadherin expression and increased DNA damage in MECs; WT but not deubiquitinase-inactive USP11 promotes luminal differentiation, DNA damage repair, and suppresses tumorigenesis. |
Usp11 KO mice, Co-IP, ubiquitination assay (site K738 identified), wild-type vs. catalytic-dead mutant overexpression, luminal differentiation marker analysis, tumor assay |
The Journal of biological chemistry |
High |
39270819
|
| 2024 |
USP11 deubiquitinates TPIT (a key transcription factor for POMC), enhancing its protein stability, which promotes POMC transcription and ACTH secretion in functioning ACTH pituitary tumors. USP11 knockdown substantially reduces POMC transcription and ACTH secretion in vitro and in vivo. |
Co-IP, ubiquitination assay, siRNA knockdown, POMC reporter assay, in vivo mouse model, ACTH ELISA |
Acta neuropathologica communications |
Medium |
39910602
|
| 2024 |
USP11 deubiquitinates OTUD5 and implicates the OTUD5-STING signaling pathway in the inflammatory response of endothelial cells after radiation-induced pneumonitis. Comprehensive proteome and ubiquitinome analyses identified USP11 overexpression as upregulating OTUD5. |
Comprehensive proteome and ubiquitinome analysis, Co-IP, western blot, Usp11 KO mouse, USP11 inhibitor (mitoxantrone), cytokine measurement |
International journal of radiation oncology, biology, physics |
Medium |
38364946
|
| 2024 |
DNMT3A stability is maintained by USP11 counteracting CUL4-DCAF8 E3 ligase-mediated degradation. USP11 also enhances DNMT3A SUMOylation by promoting DNMT3A interaction with SUMO E3 ligases and enhances DNMT3A binding to the polycomb complex, maintaining DNMT3A DNA methyltransferase activity. |
Stable USP11 expression, E1 enzyme inhibition, Co-IP, SUMOylation assay, DNA methyltransferase activity assay, subcellular localization studies |
bioRxivpreprint |
Medium |
40161590
|
| 2024 |
USP11 deubiquitinates GSK3β, modulates its Ser9 phosphorylation level, and consequently alters its enzymatic activity. USP11 deficiency protects against stress-induced synaptic injury and depressive-like behaviors by restoring synaptic protein expression in the prefrontal cortex via GSK3β/mTOR signaling. |
IP-MS, Co-IP, ubiquitination assay, phospho-GSK3β analysis, transgenic mice, primary neuronal cultures, behavioral assays (CUMS model) |
Neurobiology of stress |
Medium |
41889422
|
| 2025 |
The UBL2 domain of USP11 confers selectivity toward K48-linked polyubiquitin chains. In vitro studies with Ub-tetramers and ubiquitinated proteins demonstrate that UBL2 domain endows USP11 with K48 chain preference, an activity not observed in paralogs USP4 and USP15. |
In vitro ubiquitin chain cleavage assay (Ub-tetramers, ubiquitinated substrates), domain-deletion constructs, cell-based analysis, AI-based virtual screening for inhibitors |
The Journal of biological chemistry |
High |
41207628
|
| 2025 |
MYCBP2-SPRYD3 E3 ligase complex ubiquitinates USP11 on cysteine 318 (non-canonical ubiquitination), promoting bipolar spindle formation and mitotic slippage in the presence of microtubule-targeting drugs. This demonstrates a DUB-E3 ligase cooperation where the E3 modifies the DUB itself. |
Co-IP, ubiquitination assay (site-specific Cys318), spindle formation analysis, mitotic slippage assay, anti-microtubule drug treatment |
The Journal of biological chemistry |
Medium |
41052634
|
| 2025 |
USP11 stabilizes HINT3 via deubiquitination (reversing polyubiquitination), and HINT3 interacts with BCL2. USP11 overexpression increases BCL2 levels, contributing to endothelial apoptosis resistance in pulmonary arterial hypertension. |
Co-IP, ubiquitination assay, overexpression/knockdown, BCL2 protein level analysis, PAH patient tissue analysis |
Journal of respiratory biology and translational medicine |
Medium |
40376595
|
| 2025 |
USP11 deubiquitinates Rac1-GTP at residues K123/K147/K183, stabilizing active Rac1. Ionizing radiation (IR) activates Rac1 and induces its nuclear translocation; Rac1-GTP transcriptionally upregulates USP11, forming a self-reinforcing Rac1-USP11 feedback loop driving radioresistance in HCC. |
Co-IP, ubiquitination assay (site-specific K123/K147/K183), dual luciferase (USP11 promoter), GST pulldown, Rac1-GTP measurement, site-directed mutagenesis, colony formation, xenograft model |
British journal of cancer |
High |
41298816
|
| 2025 |
USP11 binds to PRDX2 and removes its K63-linked polyubiquitination, promoting PRDX2 translocation into the nucleus. Nuclear PRDX2 interacts with c-MYC, facilitating co-nuclear translocation and enhancing KDR (VEGFR2) transcription, activating VEGFR2 signaling and promoting angiogenesis. |
Co-IP, ubiquitination assay (K63-specific), USP11 KO in vitro and in vivo (retinal model), subcellular fractionation, ChIP (c-MYC on KDR promoter), angiogenesis assay |
Angiogenesis |
Medium |
40199774
|
| 2025 |
USP11 interacts with, deubiquitinates, and extends the half-life of SFTPC (surfactant protein C), more potently stabilizing the pathogenic I73T mutant than wild-type. USP11 depletion in hiPSC-derived alveolar organoids mitigates SFTPC-I73T-induced fibrosis; pharmacological inhibition of USP11 prevents fibrosis in TGF-β-treated organoids and bleomycin mouse model. |
CRISPR/Cas9 genome-wide DUB screen, Co-IP, TUBEs ubiquitination assay, protein half-life assay, hiPSC-derived alveolar organoid model, bleomycin mouse model, mitoxantrone (USP11 inhibitor) treatment |
Theranostics |
High |
40225577
|
| 2025 |
Usp11 sustains the survival of marginal zone B cells under ionizing radiation by deubiquitinating Notch ligands DLL1 and JAG2, regulating their ubiquitination and thereby promoting immune cell remodeling in the spleen. |
Co-IP, ubiquitination assay, Usp11 KO mouse, single-cell sequencing, flow cytometry, immunofluorescence, TBI model |
Cell death & disease |
Medium |
39904982
|