Gene Symbol: USP11
Description: ubiquitin specific peptidase 11
Alias: UHX1, ubiquitin carboxyl-terminal hydrolase 11, deubiquitinating enzyme 11, ubiquitin carboxyl-terminal hydrolase, X-linked, ubiquitin thioesterase 11, ubiquitin thiolesterase 11, ubiquitin-specific processing protease 11
Species: human
Products:     USP11

Top Publications

  1. Al Salihi M, Herhaus L, MacArtney T, Sapkota G. USP11 augments TGFβ signalling by deubiquitylating ALK5. Open Biol. 2012;2:120063 pubmed publisher
    ..In this report, we identify a deubiquitylating enzyme USP11 as an interactor of SMAD7. USP11 enhances TGFβ signalling and can override the negative effects of SMAD7...
  2. Liao T, Wu C, Su W, Jeng K, Lai M. Ubiquitination and deubiquitination of NP protein regulates influenza A virus RNA replication. EMBO J. 2010;29:3879-90 pubmed publisher
    ..We observed that downregulation of a cellular deubiquitinating enzyme USP11 resulted in enhanced virus production, suggesting that USP11 could inhibit influenza virus replication...
  3. Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X, et al. USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal. 2010;22:386-94 pubmed publisher
    ..Using a proteomic approach, we have identified Ubiquitin Specific Peptidase 11 (USP11) as an IkappaBalpha associated deubiquitinase. Overexpression of USP11 inhibits IkappaBalpha ubiquitination...
  4. Bayraktar S, Gutierrez Barrera A, Liu D, Pusztai L, Litton J, Valero V, et al. USP-11 as a predictive and prognostic factor following neoadjuvant therapy in women with breast cancer. Cancer J. 2013;19:10-7 pubmed publisher
    ..16; 95% CI, 1.16-23.07; P = 0.03). Our data indicate that USP-11 is not a predictor of a pCR after anthracycline-taxane-containing NST for breast cancer. Low USP-11 expression was independently correlated with better survival outcomes. ..
  5. Zhang L, Zhou F, Drabsch Y, Gao R, Snaar Jagalska B, Mickanin C, et al. USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-β type I receptor. Nat Cell Biol. 2012;14:717-26 pubmed publisher
    ..Moreover, AKT-induced breast cancer cell migration was inhibited by USP4 depletion and TβRI kinase inhibition. Our results uncover USP4 as an important determinant for crosstalk between TGF-β and AKT signalling pathways. ..
  6. Faesen A, Luna Vargas M, Geurink P, Clerici M, Merkx R, van Dijk W, et al. The differential modulation of USP activity by internal regulatory domains, interactors and eight ubiquitin chain types. Chem Biol. 2011;18:1550-61 pubmed publisher
    ..USPs can hydrolyze all linkages and show modest Ub-chain preferences, although some show a lack of activity toward linear di-Ub. This comprehensive kinetic analysis highlights the variability within the USP family. ..
  7. Elliott P, Liu H, Pastok M, Grossmann G, Rigden D, Clague M, et al. Structural variability of the ubiquitin specific protease DUSP-UBL double domains. FEBS Lett. 2011;585:3385-90 pubmed publisher
    ..We identified structural features that dictate different dispositions between constituent domains, which in turn may influence respective binding properties. ..
  8. Yamaguchi T, Kimura J, Miki Y, Yoshida K. The deubiquitinating enzyme USP11 controls an IkappaB kinase alpha (IKKalpha)-p53 signaling pathway in response to tumor necrosis factor alpha (TNFalpha). J Biol Chem. 2007;282:33943-8 pubmed
    ..The present studies show that a deubiquitinating enzyme, USP11, specifically regulates IkappaB kinase alpha (IKKalpha) among the NF-kappaB signaling molecules...
  9. Ideguchi H, Ueda A, Tanaka M, Yang J, Tsuji T, Ohno S, et al. Structural and functional characterization of the USP11 deubiquitinating enzyme, which interacts with the RanGTP-associated protein RanBPM. Biochem J. 2002;367:87-95 pubmed
    ..proteins by using a yeast two-hybrid method and isolated a cDNA encoding the ubiquitin-specific protease USP11. The full-length cDNA of USP11 was cloned from a Jurkat cell library...

More Information


  1. Maertens G, El Messaoudi Aubert S, Elderkin S, Hiom K, Peters G. Ubiquitin-specific proteases 7 and 11 modulate Polycomb regulation of the INK4a tumour suppressor. EMBO J. 2010;29:2553-65 pubmed publisher
    ..Here, we report that two ubiquitin-specific proteases, USP7 and USP11, co-purify with human PRC1-type complexes through direct interactions with the Psc orthologues MEL18 and BMI1, and ..
  2. Lin C, Chang H, Yu W. USP11 stabilizes HPV-16E7 and further modulates the E7 biological activity. J Biol Chem. 2008;283:15681-8 pubmed publisher
    ..Using the yeast two-hybrid system, we found that USP11 (ubiquitin-specific protease 11), a member of a protein family that cleaves polyubiquitin chains and/or ubiquitin ..
  3. Schoenfeld A, Apgar S, Dolios G, Wang R, Aaronson S. BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. Mol Cell Biol. 2004;24:7444-55 pubmed identify novel proteins that associate with the BRCA2 gene product, we found that a deubiquitinating enzyme, USP11, formed specific complexes with BRCA2...
  4. Herold S, Kalb J, Büchel G, Ade C, Baluapuri A, Xu J, et al. Recruitment of BRCA1 limits MYCN-driven accumulation of stalled RNA polymerase. Nature. 2019;: pubmed publisher
    ..Recruitment of BRCA1 requires the ubiquitin-specific protease USP11, which binds specifically to MYCN when MYCN is dephosphorylated at Thr58...
  5. Park M, Yao Y, Xia W, Setijono S, Kim J, Vila I, et al. PTEN self-regulates through USP11 via the PI3K-FOXO pathway to stabilize tumor suppression. Nat Commun. 2019;10:636 pubmed publisher unexpected role in regulating its own stability through the transcriptional upregulation of the deubiquitinase USP11 by the PI3K/FOXO pathway, and further show that this feedforward mechanism is implicated in its tumor-suppressive ..
  6. Spiliotopoulos A, Blokpoel Ferreras L, Densham R, Caulton S, Maddison B, Morris J, et al. Discovery of peptide ligands targeting a specific ubiquitin-like domain-binding site in the deubiquitinase USP11. J Biol Chem. 2019;294:424-436 pubmed publisher
    ..No such interactions have been reported for these domains in the paralog USP11, a key regulator of DNA double-strand break repair by homologous recombination...
  7. Maupin Furlow J. Putting phage to work in deubiquitinase ligand discovery. J Biol Chem. 2019;294:437-438 pubmed publisher
    ..Of the hundreds of human DUBs, USP11 has emerged as an ideal therapeutic target, as it regulates DNA double-strand break repair by homologous ..
  8. Georges A, Marcon E, Greenblatt J, Frappier L. Identification and Characterization of USP7 Targets in Cancer Cells. Sci Rep. 2018;8:15833 pubmed publisher
    ..This confirmed reported associations of USP7 with USP11, PPM1G phosphatase and TRIP12 E3 ubiquitin ligase as well as identifying novel interactions with two DEAD/DEAH-box ..
  9. Deng T, Yan G, Song X, Xie L, Zhou Y, Li J, et al. Deubiquitylation and stabilization of p21 by USP11 is critical for cell-cycle progression and DNA damage responses. Proc Natl Acad Sci U S A. 2018;115:4678-4683 pubmed publisher
    ..However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report USP11 as a deubiquitylase of p21...
  10. Marqueta Gracia J, Alvarez Alvarez M, Baeta M, Palencia Madrid L, Prieto Fernández E, Ordoñana J, et al. Differentially methylated CpG regions analyzed by PCR-high resolution melting for monozygotic twin pair discrimination. Forensic Sci Int Genet. 2018;37:e1-e5 pubmed publisher
    ..Here, we have selected 6 CpG regions located at the ITGA2B, ASPA, PDE4C, ZIC5, USP11 and NOP14 loci that have shown methylation status variation during lifetime...
  11. Lee E, Seong D, Seo J, Jeong M, Lee H, Song J. USP11-dependent selective cIAP2 deubiquitylation and stabilization determine sensitivity to Smac mimetics. Cell Death Differ. 2015;22:1463-76 pubmed publisher
    ..Ubiquitin-specific protease 11 (USP11) is a deubiquitylase that directly stabilizes cIAP2...
  12. García D, Baek C, Estrada M, Tysl T, Bennett E, Yang J, et al. USP11 Enhances TGFβ-Induced Epithelial-Mesenchymal Plasticity and Human Breast Cancer Metastasis. Mol Cancer Res. 2018;16:1172-1184 pubmed publisher
    ..Here, it is demonstrated that one DUB, ubiquitin-specific peptidase 11 (USP11), enhances TGFβ-induced EMT and self-renewal in immortalized human mammary epithelial cells...
  13. Zhang S, Xie C, Li H, Zhang K, Li J, Wang X, et al. Ubiquitin-specific protease 11 serves as a marker of poor prognosis and promotes metastasis in hepatocellular carcinoma. Lab Invest. 2018;98:883-894 pubmed publisher
    Ubiquitin-specific protease 11 (USP11) is a deubiquitinating enzyme that exerts its biological functions by regulating multiple signaling pathways such as p53, NF-κB, TGF-β, and Hippo...
  14. Kapadia B, Nanaji N, Bhalla K, Bhandary B, Lapidus R, Beheshti A, et al. Fatty Acid Synthase induced S6Kinase facilitates USP11-eIF4B complex formation for sustained oncogenic translation in DLBCL. Nat Commun. 2018;9:829 pubmed publisher
    ..Through biochemical studies, we identified eIF4B as a bonafide substrate of USP11, which stabilizes and enhances eIF4B activity...
  15. Chou C, Chang Y, Korinek M, Chen Y, Yang Y, Leu S, et al. The Regulations of Deubiquitinase USP15 and Its Pathophysiological Mechanisms in Diseases. Int J Mol Sci. 2017;18: pubmed publisher
    ..USP15 is grouped into the same category with USP4 and USP11 due to high degree of homology in an N-terminal region consisting of domains present in ubiquitin-specific ..
  16. Li N, Feng L, Han H, Yuan J, Qi X, Lian Y, et al. A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis. Cancer Lett. 2016;381:14-22 pubmed publisher
    ..The in vitro antitumor effect was RIPK1-dependent, whereas it was independent on IAPs, USP11, or EBV...
  17. Saei A, Sabatier P, Tokat Ü, Chernobrovkin A, Pirmoradian M, Zubarev R. Comparative Proteomics of Dying and Surviving Cancer Cells Improves the Identification of Drug Targets and Sheds Light on Cell Life/Death Decisions. Mol Cell Proteomics. 2018;17:1144-1155 pubmed publisher
    ..Knocking down USP11, CTTN, ACAA2, and EIF4H had anti-proliferative effects, affecting UHRF1 additionally sensitized the cells to the ..
  18. Huang R, Gorman K, Vinci C, Dobrovetsky E, Gräslund S, Kay B. Streamlining the Pipeline for Generation of Recombinant Affinity Reagents by Integrating the Affinity Maturation Step. Int J Mol Sci. 2015;16:23587-603 pubmed publisher
    ..kinase kinase 5 (MAP2K5), Splicing factor 3A subunit 1 (SF3A1) and ubiquitin carboxyl-terminal hydrolase 11 (USP11). The affinities of the resulting monobodies are typically in the single-digit nanomolar range...
  19. Xu Z, Li X, Chen J, Zhao J, Wang J, Ji Y, et al. USP11, Deubiquitinating Enzyme, Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage. J Mol Neurosci. 2016;58:16-27 pubmed publisher
    ..b>USP11, located on the X chromosome, 6 is a member of USP subclass of the DUB family...
  20. Zhao J, Wei J, Dong S, Bowser R, Zhang L, Jacko A, et al. Destabilization of Lysophosphatidic Acid Receptor 1 Reduces Cytokine Release and Protects Against Lung Injury. EBioMedicine. 2016;10:195-203 pubmed publisher
    ..The stability of LPA1 is up-regulated by ubiquitin-specific protease 11 (USP11), which deubiquitinates LPA1 and enhances LPA1-mediated pro-inflammatory effects...
  21. Vlasschaert C, Xia X, Coulombe J, Gray D. Evolution of the highly networked deubiquitinating enzymes USP4, USP15, and USP11. BMC Evol Biol. 2015;15:230 pubmed publisher
    USP4, USP15 and USP11 are paralogous deubiquitinating enzymes as evidenced by structural organization and sequence similarity...
  22. Lin Y, Jeng K, Lai M. CNOT4-Mediated Ubiquitination of Influenza A Virus Nucleoprotein Promotes Viral RNA Replication. MBio. 2017;8: pubmed publisher
    ..reported that NP is a monoubiquitinated protein which can be deubiquitinated by a cellular ubiquitin protease, USP11. In this study, we identified an E3 ubiquitin ligase, CNOT4 (Ccr4-Not transcription complex subunit 4), which can ..
  23. Lawson A, Bak D, Shannon D, Long M, Vijaykumar T, Yu R, et al. Identification of deubiquitinase targets of isothiocyanates using SILAC-assisted quantitative mass spectrometry. Oncotarget. 2017;8:51296-51316 pubmed publisher
    ..Using SILAC assisted quantitative mass spectrometry, here we identify 9 new PEITC-DUB targets: USP1, USP3, USP10, USP11, USP16, USP22, USP40, USP48 and VCPIP1...
  24. D ANDREA A, Pellman D. Deubiquitinating enzymes: a new class of biological regulators. Crit Rev Biochem Mol Biol. 1998;33:337-52 pubmed
    ..Here we explore the structural and biochemical properties of deubiquitinating enzymes and their emerging roles as cellular switches. ..
  25. Stoddart K, Jermak C, Nagaraja R, Schlessinger D, Bech Hansen N. Physical map covering a 2 Mb region in human xp11.3 distal to DX6849. Gene. 1999;227:111-6 pubmed
    ..The contig is merged with published physical maps both in the distal and in the centromeric direction of Xp, and provides reagents to aid in the DNA sequencing and the finding of genes in this region of the human genome. ..
  26. Liu T, Yu J, Deng M, Yin Y, Zhang H, Luo K, et al. CDK4/6-dependent activation of DUB3 regulates cancer metastasis through SNAIL1. Nat Commun. 2017;8:13923 pubmed publisher
    ..Overall, our study establishes the CDK4/6-DUB3 axis as an important regulatory mechanism of breast cancer metastasis and provides a rationale for potential therapeutic interventions in the treatment of breast cancer metastasis. ..
  27. Ma H, Chen H, Guo X, Wang Z, Sowa M, Zheng L, et al. M phase phosphorylation of the epigenetic regulator UHRF1 regulates its physical association with the deubiquitylase USP7 and stability. Proc Natl Acad Sci U S A. 2012;109:4828-33 pubmed publisher
    ..These findings identify a molecular mechanism by which cellular UHRF1 level is regulated, which may impact cell proliferation. ..
  28. Ke J, Dai C, Wu W, Gao J, Xia A, Liu G, et al. USP11 regulates p53 stability by deubiquitinating p53. J Zhejiang Univ Sci B. 2014;15:1032-8 pubmed publisher
    ..To better understand the regulation of p53, we tested the interaction between p53 and USP11 using co-immunoprecipitation...
  29. Lim K, Suresh B, Park J, Kim Y, Ramakrishna S, Baek K. Ubiquitin-specific protease 11 functions as a tumor suppressor by modulating Mgl-1 protein to regulate cancer cell growth. Oncotarget. 2016;7:14441-57 pubmed publisher
    ..Here, we analyzed the ability of ubiquitin-specific protease 11 (USP11) as a novel regulator of Mgl-1 and it requires RanBPM to regulate proteasomal degradation of Mgl-1...
  30. Swanson D, Freund C, Ploder L, McInnes R, Valle D. A ubiquitin C-terminal hydrolase gene on the proximal short arm of the X chromosome: implications for X-linked retinal disorders. Hum Mol Genet. 1996;5:533-8 pubmed
    ..Additionally, there is evidence that members of the ubiquitin hydrolase family may play a role in oncogenesis and a locus implicated in ovarian cancer is also located within this region. ..
  31. Brandau O, Nyakatura G, Jedele K, Platzer M, Achatz H, Ross M, et al. UHX1 and PCTK1: precise characterisation and localisation within a gene-rich region in Xp11.23 and evaluation as candidate genes for retinal diseases mapped to Xp21.1-p11.2. Eur J Hum Genet. 1998;6:459-66 pubmed
    The gene for ubiquitin hydrolase on the X chromosome (UHX1), cloned and mapped to Xp21.2-p11.2, is a candidate gene for retinal diseases...
  32. Stockum A, Snijders A, Maertens G. USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation. PLoS ONE. 2018;13:e0190513 pubmed publisher
    ..spindle formation, as a novel substrate of the deubiquitinating enzyme (DUB) Ubiquitin Specific Protease 11 (USP11)...
  33. Shah P, Qiang L, Yang S, Soltani K, He Y. Regulation of XPC deubiquitination by USP11 in repair of UV-induced DNA damage. Oncotarget. 2017;8:96522-96535 pubmed publisher
    ..Here we show that ubiquitin-specific peptidase 11 (USP11) positively regulates NER by deubiquitinating xeroderma pigmentosum complementation group C (XPC) and promoting ..
  34. Orthwein A, Noordermeer S, Wilson M, Landry S, Enchev R, Sherker A, et al. A mechanism for the suppression of homologous recombination in G1 cells. Nature. 2015;528:422-6 pubmed publisher
    ..6). PALB2 ubiquitylation suppresses its interaction with BRCA1 and is counteracted by the deubiquitylase USP11, which is itself under cell cycle control...
  35. Angelats C, Wang X, Jermiin L, Copeland N, Jenkins N, Baker R. Isolation and characterization of the mouse ubiquitin-specific protease Usp15. Mamm Genome. 2003;14:31-46 pubmed
    ..Phylogenetic studies suggest that a sequence currently identified as a chicken Usp4 ortholog is in fact a USP15 ortholog, while bona-fide chicken, cow, and rat Usp4 orthologs can be identified in EST databases. ..
  36. Zhang E, Shen B, Mu X, Qin Y, Zhang F, Liu Y, et al. Ubiquitin-specific protease 11 (USP11) functions as a tumor suppressor through deubiquitinating and stabilizing VGLL4 protein. Am J Cancer Res. 2016;6:2901-2909 pubmed
    ..In this study, we identify deubiquitinating enzyme USP11 as a novel VGLL4 interactor...
  37. Jacko A, Nan L, Li S, Tan J, Zhao J, Kass D, et al. De-ubiquitinating enzyme, USP11, promotes transforming growth factor β-1 signaling through stabilization of transforming growth factor β receptor II. Cell Death Dis. 2016;7:e2474 pubmed publisher
    ..Here we reveal that a de-ubiquitinating enzyme, USP11, promotes TGFβ-1 signaling through de-ubiquitination and stabilization of TβRII...
  38. Hendriks I, Schimmel J, Eifler K, Olsen J, Vertegaal A. Ubiquitin-specific Protease 11 (USP11) Deubiquitinates Hybrid Small Ubiquitin-like Modifier (SUMO)-Ubiquitin Chains to Counteract RING Finger Protein 4 (RNF4). J Biol Chem. 2015;290:15526-37 pubmed publisher
    ..Using a proteomic approach, we identified the deubiquitinating enzyme ubiquitin-specific protease 11 (USP11), a known DDR-component, as a functional interactor of RNF4...
  39. Zhou Z, Luo A, Shrivastava I, He M, Huang Y, Bahar I, et al. Regulation of XIAP Turnover Reveals a Role for USP11 in Promotion of Tumorigenesis. EBioMedicine. 2017;15:48-61 pubmed publisher
    ..This led to the identification of USP11 as a critical determinant of mammary tumor initiation and progression...
  40. Wang D, Zhao J, Li S, Wei J, Nan L, Mallampalli R, et al. Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene expression and activate lung epithelial cells. J Mol Cell Biol. 2017;:1-14 pubmed publisher
    ..of E2F1 by GSK3? increases E2F1 association with the deubiquitinating enzyme, ubiquitin-specific protease 11 (USP11), which removes K63-linked ubiquitin chains thereby preventing E2F1 degradation in the nuclei...
  41. Yu M, Liu K, Mao Z, Luo J, Gu W, Zhao W. USP11 Is a Negative Regulator to γH2AX Ubiquitylation by RNF8/RNF168. J Biol Chem. 2016;291:959-67 pubmed publisher
    ..Here, we found that RNF8/RNF168 ubiquitylates γH2AX. We identified that USP11 is a unique deubiquitylation enzyme for γH2AX...
  42. Harper S, Gratton H, Cornaciu I, Oberer M, Scott D, Emsley J, et al. Structure and catalytic regulatory function of ubiquitin specific protease 11 N-terminal and ubiquitin-like domains. Biochemistry. 2014;53:2966-78 pubmed publisher
    The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFβ signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity...
  43. Wu H, Lin Y, Liu C, Chung H, Wang Y, Lin Y, et al. USP11 regulates PML stability to control Notch-induced malignancy in brain tumours. Nat Commun. 2014;5:3214 pubmed publisher
    ..Here we identify USP11 as a PML regulator by RNAi screening...
  44. Thiselton D, McDowall J, Brandau O, Ramser J, d Esposito F, Bhattacharya S, et al. An integrated, functionally annotated gene map of the DXS8026-ELK1 interval on human Xp11.3-Xp11.23: potential hotspot for neurogenetic disorders. Genomics. 2002;79:560-72 pubmed
    ..positioning 10 polymorphic microsatellites (one of which is novel), 16 ESTs, and 12 known genes (RP2, PCTK1, UHX1, UBE1, RBM10, ZNF157, SYN1, ARAF1, TIMP1, PFC, ELK1, UXT)...