USP8

Summary

Gene Symbol: USP8
Description: ubiquitin specific peptidase 8
Alias: HumORF8, PITA4, SPG59, UBPY, ubiquitin carboxyl-terminal hydrolase 8, deubiquitinating enzyme 8, ubiquitin isopeptidase Y, ubiquitin thiolesterase 8, ubiquitin-specific-processing protease 8
Species: human
Products:     USP8

Top Publications

  1. Berlin I, Schwartz H, Nash P. Regulation of epidermal growth factor receptor ubiquitination and trafficking by the USP8·STAM complex. J Biol Chem. 2010;285:34909-21 pubmed publisher
    ..The deubiquitinating enzyme ubiquitin-specific protease 8 (USP8/UBPy) has been previously implicated in the regulation of the epidermal growth factor receptor (EGFR); however, the ..
  2. Li S, Chen Y, Shi Q, Yue T, Wang B, Jiang J. Hedgehog-regulated ubiquitination controls smoothened trafficking and cell surface expression in Drosophila. PLoS Biol. 2012;10:e1001239 pubmed publisher
    ..Finally, we show that Smo ubiquitination is counteracted by the deubiquitinating enzyme UBPY/USP8. Gain and loss of UBPY lead to reciprocal changes in Smo cell surface expression...
  3. Mizuno E, Iura T, Mukai A, Yoshimori T, Kitamura N, Komada M. Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes. Mol Biol Cell. 2005;16:5163-74 pubmed
    ..Here, we describe the role of a deubiquitinating enzyme UBPY/USP8 in the down-regulation of epidermal growth factor (EGF) receptor (EGFR)...
  4. Row P, Liu H, Hayes S, Welchman R, Charalabous P, Hofmann K, et al. The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. J Biol Chem. 2007;282:30929-37 pubmed
    ..characterized a Microtubule Interacting and Transport (MIT) domain at the N terminus of the deubiquitinating enzyme UBPY/USP8...
  5. Mizuno E, Kitamura N, Komada M. 14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase. Exp Cell Res. 2007;313:3624-34 pubmed
    The deubiquitinating enzyme UBPY, also known as USP8, regulates cargo sorting and membrane traffic at early endosomes. Here we demonstrate the regulatory mechanism of the UBPY catalytic activity...
  6. Naviglio S, Mattecucci C, Matoskova B, Nagase T, Nomura N, Di Fiore P, et al. UBPY: a growth-regulated human ubiquitin isopeptidase. EMBO J. 1998;17:3241-50 pubmed
    ..We have identified and characterized a novel human ubiquitin isopeptidase, UBPY, which both as a recombinant protein and upon immunoprecipitation from cell extracts is able to cleave linear or ..
  7. Mukai A, Yamamoto Hino M, Awano W, Watanabe W, Komada M, Goto S. Balanced ubiquitylation and deubiquitylation of Frizzled regulate cellular responsiveness to Wg/Wnt. EMBO J. 2010;29:2114-25 pubmed publisher
    ..cells and in Drosophila, and that the cell surface level of Frizzled is regulated by deubiquitylating enzyme UBPY/ubiquitin-specific protease 8 (USP8)...
  8. Xia R, Jia H, Fan J, Liu Y, Jia J. USP8 promotes smoothened signaling by preventing its ubiquitination and changing its subcellular localization. PLoS Biol. 2012;10:e1001238 pubmed publisher
    ..Using an in vivo RNAi screen, we identified ubiquitin-specific protease 8 (USP8) as a deubiquitinase that down-regulates Smo ubiquitination...
  9. Byun S, Lee S, Lee J, Jeong C, Farrand L, Lim S, et al. USP8 is a novel target for overcoming gefitinib resistance in lung cancer. Clin Cancer Res. 2013;19:3894-904 pubmed publisher
    ..Our purpose was to test ubiquitin-specific peptidase 8 (USP8) as a potential therapeutic target for gefitinib-resistant and -sensitive non-small cell lung cancer (NSCLC)...

More Information

Publications112 found, 100 shown here

  1. Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F, et al. Mutations in the deubiquitinase gene USP8 cause Cushing's disease. Nat Genet. 2015;47:31-8 pubmed publisher
    ..We found somatic mutations in the USP8 deubiquitinase gene in 4 of 10 adenomas...
  2. Gu H, Shi X, Liu C, Wang C, Sui N, Zhao Y, et al. USP8 maintains embryonic stem cell stemness via deubiquitination of EPG5. Nat Commun. 2019;10:1465 pubmed publisher
    ..We identify that the deubiquitinating enzyme USP8 binds to the Coiled-coil domain of EPG5...
  3. Scotti E, Calamai M, Goulbourne C, Zhang L, Hong C, Lin R, et al. IDOL stimulates clathrin-independent endocytosis and multivesicular body-mediated lysosomal degradation of the low-density lipoprotein receptor. Mol Cell Biol. 2013;33:1503-14 pubmed publisher
    ..We further show that USP8 acts downstream of IDOL to deubiquitinate LDLR and that USP8 is required for LDLR entry into the MVB pathway...
  4. Crespo Yanez X, Aguilar Gurrieri C, Jacomin A, Journet A, Mortier M, Taillebourg E, et al. CHMP1B is a target of USP8/UBPY regulated by ubiquitin during endocytosis. PLoS Genet. 2018;14:e1007456 pubmed publisher
    ..We demonstrate further that CHMP1B is deubiquitinated by the ubiquitin specific protease USP8 (syn...
  5. Losa M, Mortini P, Pagnano A, Detomas M, Cassarino M, Pecori Giraldi F. Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas. Endocrine. 2019;63:240-246 pubmed publisher
    somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been described in patients with Cushing's disease (CD)...
  6. Macdonald E, Urbé S, Clague M. USP8 controls the trafficking and sorting of lysosomal enzymes. Traffic. 2014;15:879-88 pubmed publisher
    The endosomal deubiquitylase USP8 has profound effects on endosomal morphology and organisation. Previous reports have proposed both positive (EGFR, MET) and negative roles in the down-regulation of receptors (Frizzled, Smoothened)...
  7. Sun J, Hu Q, Peng H, Peng C, Zhou L, Lu J, et al. The ubiquitin-specific protease USP8 deubiquitinates and stabilizes Cx43. J Biol Chem. 2018;293:8275-8284 pubmed publisher
    ..Here, we report that the ubiquitin-specific peptidase 8 (USP8) interacts with and deubiquitinates Cx43...
  8. Chen J, Jian X, Deng S, Ma Z, Shou X, Shen Y, et al. Identification of recurrent USP48 and BRAF mutations in Cushing's disease. Nat Commun. 2018;9:3171 pubmed publisher
    ..Mutations of the deubiquitinase gene USP8 occur in 35-62% of corticotroph adenomas...
  9. Marques P, Korbonits M. Genetic Aspects of Pituitary Adenomas. Endocrinol Metab Clin North Am. 2017;46:335-374 pubmed publisher
    ..Sporadic adenomas represent the vast majority of the cases, where recognized somatic mutations (eg, GNAS or USP8), as well as altered gene-expression profile often affecting cell cycle proteins have been identified...
  10. Kerrisk Campbell M, Sheng M. USP8 Deubiquitinates SHANK3 to Control Synapse Density and SHANK3 Activity-Dependent Protein Levels. J Neurosci. 2018;38:5289-5301 pubmed publisher
    ..Here we identify USP8/UBPY as a deubiquitinating enzyme that regulates SHANK3 and SHANK1 ubiquitination and protein levels...
  11. Zheng Y, Liu Q, Wu Y, Ma L, Zhang Z, Liu T, et al. Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis. EMBO J. 2018;37: pubmed publisher
    ..NS1 recruits the host deubiquitinase USP8 to cleave K11-linked poly-ubiquitin chains from caspase-1 at Lys134, thus inhibiting the proteasomal degradation of ..
  12. Pradhan Sundd T, Verheyen E. The Myopic-Ubpy-Hrs nexus enables endosomal recycling of Frizzled. Mol Biol Cell. 2015;26:3329-42 pubmed publisher
    ..Overexpression of Hrs rescues the trafficking defect caused by mop knockdown. Mop aids in the maintenance of Ubpy, which deubiquitinates (and thus stabilizes) Hrs. In the absence of the ubiquitin ligase Cbl, Mop is dispensable...
  13. Assie G. Genomic insights into Cushing syndrome. Ann Endocrinol (Paris). 2018;79:119-122 pubmed publisher
    ..carcinomas, PRKACA in cortisol-producing adrenal adenomas, ARMC5 in primary macronodular adrenal hyperplasia and USP8 in pituitary corticotroph adenomas. These genes shed new lights on the mechanisms responsible for these tumors...
  14. Kim Y, Shiba Ishii A, Nakagawa T, Iemura S, Natsume T, Nakano N, et al. Stratifin regulates stabilization of receptor tyrosine kinases via interaction with ubiquitin-specific protease 8 in lung adenocarcinoma. Oncogene. 2018;37:5387-5402 pubmed publisher
    ..Here, pull-down assay and LC-MS/MS analysis revealed that ubiquitin-specific protease 8 (USP8) specifically bound to SFN in lung adenocarcinoma cells...
  15. Kato M, Miyazawa K, Kitamura N. A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP. J Biol Chem. 2000;275:37481-7 pubmed
    ..Ubiquitination of growth factor receptors is thought to regulate their intracellular degradation. Thus, UBPY may play a regulatory role in the degradation by interaction with the SH3 domain of Hbp via the novel SH3-binding ..
  16. Ge C, Che L, Ren J, Pandita R, Lu J, Li K, et al. BRUCE regulates DNA double-strand break response by promoting USP8 deubiquitination of BRIT1. Proc Natl Acad Sci U S A. 2015;112:E1210-9 pubmed publisher
    ..We show mechanistically that BRUCE acts as a scaffold, bridging the ubiquitin-specific peptidase 8 (USP8) and BRIT1 in a complex to coordinate USP8-catalyzed deubiquitination of BRIT1...
  17. Kawaguchi K, Endo A, Fukushima T, Madoka Y, Tanaka T, Komada M. Ubiquitin-specific protease 8 deubiquitinates Sec31A and decreases large COPII carriers and collagen IV secretion. Biochem Biophys Res Commun. 2018;499:635-641 pubmed publisher
    ..However, the deubiquitinating enzyme for Sec31A was unclear. Here, we show that the deubiquitinating enzyme USP8 interacts with and deubiquitinates Sec31A. The interaction was mediated by the adaptor protein STAM1...
  18. Ceriani M, Amigoni L, D Aloia A, Berruti G, Martegani E. The deubiquitinating enzyme UBPy/USP8 interacts with TrkA and inhibits neuronal differentiation in PC12 cells. Exp Cell Res. 2015;333:49-59 pubmed publisher
    ..In this study we demonstrated that in PC12 cells the TrkA receptor interacts with the deubiquitinating enzyme USP8/UBPy in a NGF-dependent manner and that it is deubiquitinated in vivo and in vitro by USP8...
  19. Durcan T, Fon E. The three 'P's of mitophagy: PARKIN, PINK1, and post-translational modifications. Genes Dev. 2015;29:989-99 pubmed publisher
    ..are reversible and can be disassembled by deubiquitinating enzymes (DUBs), including Ub-specific protease 8 (USP8), USP15, and USP30...
  20. Agromayor M, Carlton J, Phelan J, Matthews D, Carlin L, Ameer Beg S, et al. Essential role of hIST1 in cytokinesis. Mol Biol Cell. 2009;20:1374-87 pubmed publisher
    ..is necessary for its interaction with VPS4, LIP5 and other MIT domain-containing proteins, namely, MITD1, AMSH, UBPY, and Spastin...
  21. Masschaele D, De Ceuninck L, Wauman J, Defever D, Stenner F, Lievens S, et al. RNF41 interacts with the VPS52 subunit of the GARP and EARP complexes. PLoS ONE. 2017;12:e0178132 pubmed publisher
    ..directly ubiquitinate ErbB3, IL-3, EPO and RAR? receptors or downstream signaling molecules such as Myd88, TBK1 and USP8. In this way it can regulate receptor signaling and routing...
  22. Zhang J, Zhang P, Wei Y, Piao H, Wang W, Maddika S, et al. Deubiquitylation and stabilization of PTEN by USP13. Nat Cell Biol. 2013;15:1486-1494 pubmed publisher
    ..These findings identify USP13 as a tumour-suppressing protein that functions through deubiquitylation and stabilization of PTEN. ..
  23. Scudder S, Goo M, Cartier A, Molteni A, Schwarz L, Wright R, et al. Synaptic strength is bidirectionally controlled by opposing activity-dependent regulation of Nedd4-1 and USP8. J Neurosci. 2014;34:16637-49 pubmed publisher
    ..show that NMDAR activation causes the rapid dephosphorylation and activation of the deubiquitinating enzyme (DUB) USP8. Surface AMPAR levels and synaptic strength are inversely regulated by Nedd4-1 and USP8...
  24. Berruti G, Paiardi C. USP8/UBPy-regulated sorting and the development of sperm acrosome: the recruitment of MET. Reproduction. 2015;149:633-44 pubmed publisher
    ..The trafficking sorted by USP8/UBPy, an endosomal regulator recently described as a compelling candidate for male fertility gene, was investigated ..
  25. Qu C, Kunkalla K, Vaghefi A, Frederiksen J, Liu Y, Chapman J, et al. Smoothened stabilizes and protects TRAF6 from degradation: A novel non-canonical role of smoothened with implications in lymphoma biology. Cancer Lett. 2018;436:149-158 pubmed publisher
    ..In summary, our study reveals a novel cell survival mechanism in which SMO stabilizes and protects TRAF6 from degradation. The axis SMO/TRAF6/AKT is highly relevant in the biology of DLBCL and is involved in doxorubicin resistance. ..
  26. Jian F, Cao Y, Bian L, Sun Q. USP8: a novel therapeutic target for Cushing's disease. Endocrine. 2015;50:292-6 pubmed publisher
    ..Recently, the recurrent activating mutations in the gene encoding ubiquitin-specific protease 8 (USP8) in CD have been independently reported by two teams...
  27. Perez Rivas L, Reincke M. Genetics of Cushing's disease: an update. J Endocrinol Invest. 2016;39:29-35 pubmed publisher
    ..sequencing, recurrent mutations have been reported in the gene coding for the ubiquitin-specific protease 8 (USP8), a protein with deubiquitinase (DUB) activity that modulates the lysosomal turnover of the EGF receptor (EGFR) and ..
  28. Kathman S, Span I, Smith A, Xu Z, Zhan J, Rosenzweig A, et al. A Small Molecule That Switches a Ubiquitin Ligase From a Processive to a Distributive Enzymatic Mechanism. J Am Chem Soc. 2015;137:12442-5 pubmed publisher
    ..complex, is able to synthesize polyubiquitin chains on the substrate in the presence of the deubiquitinating enzyme USP8. Therefore, inhibition of E3 ligase processivity is a viable strategy to design E3 inhibitors...
  29. Bi W, Larsen A, Dunn I. Genomic Alterations in Sporadic Pituitary Tumors. Curr Neurol Neurosci Rep. 2018;18:4 pubmed publisher
    ..occur largely in subsets of hormone-producing tumors, including GNAS and GPR101 in somatotroph adenomas and USP8 in corticotroph adenomas...
  30. Wauer T, Swatek K, Wagstaff J, Gladkova C, Pruneda J, Michel M, et al. Ubiquitin Ser65 phosphorylation affects ubiquitin structure, chain assembly and hydrolysis. EMBO J. 2015;34:307-25 pubmed publisher
    ..is recognized by the TAB2 NZF Ub binding domain (UBD), 10 out of 12 deubiquitinases (DUBs), including USP8, USP15 and USP30, are impaired in hydrolyzing phosphoUb chains...
  31. Sbiera S, Tryfonidou M, Weigand I, Grinwis G, Broeckx B, Herterich S, et al. Lack of Ubiquitin Specific Protease 8 (USP8) Mutations in Canine Corticotroph Pituitary Adenomas. PLoS ONE. 2016;11:e0169009 pubmed publisher
    ..Recently, hotspot recurrent mutations in the gene encoding for ubiquitin specific protease 8 (USP8) have been identified as the main driver behind the formation of ACTH-secreting pituitary adenomas in humans...
  32. Meijer I, Kerperien J, Sotoca A, van Zoelen E, van Leeuwen J. The Usp8 deubiquitination enzyme is post-translationally modified by tyrosine and serine phosphorylation. Cell Signal. 2013;25:919-30 pubmed publisher
    ..Before incorporation into MVBs, the EGFR is deubiquitinated by Usp8. We previously demonstrated that Usp8 is tyrosine phosphorylated in an EGFR- and SRC-kinase dependent manner...
  33. Warner N, Burberry A, Pliakas M, McDonald C, Núñez G. A genome-wide small interfering RNA (siRNA) screen reveals nuclear factor-κB (NF-κB)-independent regulators of NOD2-induced interleukin-8 (IL-8) secretion. J Biol Chem. 2014;289:28213-24 pubmed publisher
    ..Using immortalized macrophages, we validate the ubiquitin protease, USP8, and the endosomal sorting protein, VPS28, as negative regulators of NOD2-induced cytokine secretion...
  34. Trivellin G, Correa R, Batsis M, Faucz F, Chittiboina P, Bjelobaba I, et al. Screening for GPR101 defects in pediatric pituitary corticotropinomas. Endocr Relat Cancer. 2016;23:357-365 pubmed
    ..Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still ..
  35. Adoro S, Park K, Bettigole S, Lis R, Shin H, Seo H, et al. Post-translational control of T cell development by the ESCRT protein CHMP5. Nat Immunol. 2017;18:780-790 pubmed publisher
    ..positive selection resulted in the stabilization of CHMP5 by inducing its interaction with the deubiquitinase USP8. Our results thus identify CHMP5 as an essential component of the post-translational machinery required for T cell ..
  36. Row P, Prior I, McCullough J, Clague M, Urbé S. The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation. J Biol Chem. 2006;281:12618-24 pubmed
    b>UBPY is a ubiquitin-specific protease that can deubiquitinate monoubiquitinated receptor tyrosine kinases, as well as process Lys-48- and Lys-63-linked polyubiquitin to lower denomination forms in vitro...
  37. Cao Z, Wu X, Yen L, Sweeney C, Carraway K. Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1. Mol Cell Biol. 2007;27:2180-8 pubmed
    ..that treatment of cells with the ErbB3 ligand neuregulin-1 (NRG1) stabilizes the deubiquitinating enzyme USP8, which in turn stabilizes Nrdp1. The catalytic activity of USP8 is required for NRG1-induced Nrdp1 stabilization...
  38. Theodoropoulou M, Reincke M, Fassnacht M, Komada M. Decoding the genetic basis of Cushing's disease: USP8 in the spotlight. Eur J Endocrinol. 2015;173:M73-83 pubmed publisher
    ..Recently, a somatic mutational hotspot was found in up to half of corticotrophinomas in the USP8 gene that encodes a protein that impairs the downregulation of the epidermal growth factor receptor (EGFR) and ..
  39. Sbiera S, Deutschbein T, Weigand I, Reincke M, Fassnacht M, Allolio B. The New Molecular Landscape of Cushing's Disease. Trends Endocrinol Metab. 2015;26:573-83 pubmed publisher
    ..Most recently, mutations in the gene of ubiquitin-specific peptidase 8 (USP8) increasing its deubiquination activity were discovered in a high percentage of corticotroph adenomas...
  40. Mukai A, Mizuno E, Kobayashi K, Matsumoto M, Nakayama K, Kitamura N, et al. Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis. J Cell Sci. 2008;121:1325-33 pubmed publisher
    ..Two deubiquitylating enzymes UBPY and AMSH, which act on endosomes in interphase, were also recruited to the cleavage region...
  41. Yeates E, Tesco G. The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation. J Biol Chem. 2016;291:15753-66 pubmed publisher
    ..The ubiquitin-specific peptidase 8 (USP8), an endosome-associated deubiquitinating enzyme, regulates the ubiquitination, trafficking, and lysosomal ..
  42. Baykara M, Yaman M, Buyukberber S, Tufan G, Demirci U, Benekli M, et al. Clinical and prognostic importance of XIAP and USP8 in advanced stages of non-small cell lung cancer. J BUON. 2013;18:921-7 pubmed
    ..relationship of the apoptosis regulators X-linked inhibitor of apoptosis (XIAP) and ubiquitin specific protease 8 (USP8) with clinical parameters, survival and response to chemotherapy in patients with advanced stages of non-small cell ..
  43. Mizuno E, Kobayashi K, Yamamoto A, Kitamura N, Komada M. A deubiquitinating enzyme UBPY regulates the level of protein ubiquitination on endosomes. Traffic. 2006;7:1017-31 pubmed
    ..E Vps protein complex essential for the initial step of the sorting pathway, binds two deubiquitinating enzymes, UBPY and AMSH. Here we examined the effects of inactivating UBPY on protein ubiquitination at endosomes...
  44. Caimari F, Korbonits M. Novel Genetic Causes of Pituitary Adenomas. Clin Cancer Res. 2016;22:5030-5042 pubmed
    ..of growth hormone- and adrenocorticotrophin-secreting adenomas have activating somatic mutations in the GNAS and USP8 genes, respectively. Rarely, germline mutations predispose to pituitary tumorigenesis, often in a familial setting...
  45. Jacomin A, Bescond A, Soleilhac E, Gallet B, Schoehn G, Fauvarque M, et al. The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila. PLoS ONE. 2015;10:e0143078 pubmed publisher
    ..This screen identified Uch-L3, Usp45, Usp12 and Ubpy. In this paper, we show that Ubpy loss of function results in the accumulation of autophagosomes due to a blockade ..
  46. Gioria M, Pasini M, Berruti G. Dynamic of contribution of UBPy-sorted cargo to acrosome biogenesis: effects of its derailment in a mouse model of globozoospermia, the infertile Vps54 (L967Q) mutant. Cell Tissue Res. 2017;369:413-427 pubmed publisher
    ..The chosen proteins of this study were UBPy (ESCRT-DUB), together with endosome compartment markers EEA1 and pallidin...
  47. Kasahara K, Aoki H, Kiyono T, Wang S, Kagiwada H, Yuge M, et al. EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase. Nat Commun. 2018;9:758 pubmed publisher
    ..growth factor receptor (EGFR) kinase suppresses ciliogenesis by directly phosphorylating the deubiquitinase USP8 on Tyr-717 and Tyr-810 in RPE1 cells...
  48. 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. ..
  49. Ernst A, Avvakumov G, Tong J, Fan Y, Zhao Y, Alberts P, et al. A strategy for modulation of enzymes in the ubiquitin system. Science. 2013;339:590-5 pubmed publisher
    ..Last, we showed that ubiquitin variants can bind selectively to ubiquitin-binding domains. Ubiquitin variants exhibit selective function in cells and thus enable orthogonal modulation of specific enzymatic steps in the ubiquitin system. ..
  50. Jacomin A, Fauvarque M, Taillebourg E. A functional endosomal pathway is necessary for lysosome biogenesis in Drosophila. BMC Cell Biol. 2016;17:36 pubmed
    ..We previously identified the deubiquitinating enzyme UBPY/USP8 as being necessary for lysosomal biogenesis and productive autophagy in Drosophila...
  51. 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. ..
  52. Ali N, Zhang L, Taylor S, Mironov A, Urbé S, Woodman P. Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB. Curr Biol. 2013;23:453-61 pubmed publisher
    ..that the ESCRT accessory protein HD-PTP/PTPN23 associates with EGFR and combines with the deubiquitinating enzyme UBPY/USP8 to transfer EGFR from ESCRT-0 to ESCRT-III and drive EGFR sorting to intralumenal vesicles...
  53. Durcan T, Fon E. USP8 and PARK2/parkin-mediated mitophagy. Autophagy. 2015;11:428-9 pubmed publisher
    ..Moreover, PARK2 interacts with the deubiquitinating enzyme USP8 that preferentially removes these K6-linked conjugates, thereby regulating the activity and function of PARK2 in ..
  54. Ding M, Li L, Ding X, Ren H, Zhong R. [Study on the association of USP8 gene polymorphisms with male infertility in ethnic Han Chinese from Sichuan]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2015;32:269-73 pubmed publisher
    To assess the association of single nucleotide polymorphisms (SNPs) of ubiquitin-specific protease 8 gene (USP8) with male infertility among ethnic Han Chinese from Sichuan...
  55. Ma G, Li S, Han Y, Li S, Yue T, Wang B, et al. Regulation of Smoothened Trafficking and Hedgehog Signaling by the SUMO Pathway. Dev Cell. 2016;39:438-451 pubmed publisher
    ..Sumoylation of Smo in turn recruits a deubiquitinase UBPY/USP8 to antagonize Smo ubiquitination and degradation, leading to its cell-surface accumulation and elevated Hh pathway ..
  56. Wu X, Yen L, Irwin L, Sweeney C, Carraway K. Stabilization of the E3 ubiquitin ligase Nrdp1 by the deubiquitinating enzyme USP8. Mol Cell Biol. 2004;24:7748-57 pubmed
    ..Using affinity chromatography, we identified the deubiquitinating enzyme USP8 (also called Ubpy) as a protein that physically interacts with Nrdp1...
  57. Avvakumov G, Walker J, Xue S, Finerty P, MacKenzie F, Newman E, et al. Amino-terminal dimerization, NRDP1-rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8). J Biol Chem. 2006;281:38061-70 pubmed
    Ubiquitin-specific protease 8 (USP8) hydrolyzes mono and polyubiquitylated targets such as epidermal growth factor receptors and is involved in clathrin-mediated internalization...
  58. Pohl C, Jentsch S. Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell. 2008;132:832-45 pubmed publisher
    ..We propose that BRUCE coordinates multiple steps required for abscission and that ubiquitylation may be a crucial trigger. ..
  59. Meijer I, van Rotterdam W, van Zoelen E, van Leeuwen J. Cbl and Itch binding sites in ERBB4 CYT-1 and CYT-2 mediate K48- and K63-polyubiquitination, respectively. Cell Signal. 2013;25:470-8 pubmed publisher
    ..by the K63 polyubiquitin-specific AMSH deubiquitinating enzyme, while CYT-1 is slightly deubiquitinated by USP8. We conclude that Cbl and Itch binding sites in ERBB4 CYT-1 and CYT-2 mediate K48- and K63-polyubiquitination, ..
  60. Janssen J, Schleithoff L, Bartram C, Schulz A. An oncogenic fusion product of the phosphatidylinositol 3-kinase p85beta subunit and HUMORF8, a putative deubiquitinating enzyme. Oncogene. 1998;16:1767-72 pubmed
    ..Sequence analysis revealed a fusion product of the p85beta subunit of phosphatidylinositol (PI) 3-kinase and HUMORF8, a putative deubiquitinating enzyme, which has been generated during the DNA transfection process...
  61. Lange A, Ismail M, Rivière G, Hologne M, Lacabanne D, Guillière F, et al. Competitive binding of UBPY and ubiquitin to the STAM2 SH3 domain revealed by NMR. FEBS Lett. 2012;586:3379-84 pubmed publisher
    ..and UIM domains, while the SH3 domain of STAM2 was reported to interact with deubiquitinating enzymes (DUBs) like UBPY and AMSH...
  62. Zhou R, Tomkovicz V, Butler P, Ochoa L, Peterson Z, Snyder P. Ubiquitin-specific peptidase 8 (USP8) regulates endosomal trafficking of the epithelial Na+ channel. J Biol Chem. 2013;288:5389-97 pubmed publisher
    ..In this work, we identified a role for USP8 in the control of ENaC ubiquitination and trafficking...
  63. Dufner A, Kisser A, Niendorf S, Basters A, Reissig S, Schönle A, et al. The ubiquitin-specific protease USP8 is critical for the development and homeostasis of T cells. Nat Immunol. 2015;16:950-60 pubmed publisher
    ..Here we identified the ubiquitin-specific protease USP8 as a regulatory component of the T cell antigen receptor (TCR) signalosome that interacted with the adaptor Gads ..
  64. Alexopoulou Z, Lang J, Perrett R, Elschami M, Hurry M, Kim H, et al. Deubiquitinase Usp8 regulates ?-synuclein clearance and modifies its toxicity in Lewy body disease. Proc Natl Acad Sci U S A. 2016;113:E4688-97 pubmed publisher
    ..in cells with Lewy bodies inversely correlated with the content and pathological localization of the deubiquitinase Usp8. Usp8 interacted and partly colocalized with ?-synuclein in endosomal membranes and, both in cells and after ..
  65. Harkiolaki M, Lewitzky M, Gilbert R, Jones E, Bourette R, Mouchiroud G, et al. Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76. EMBO J. 2003;22:2571-82 pubmed
    ..Interestingly, the SH3C displays ion-dependent dimerization in the crystal and in solution, suggesting a novel mechanism for the regulation of SH3 domain functions. ..
  66. Harkiolaki M, Tsirka T, Lewitzky M, Simister P, Joshi D, Bird L, et al. Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. Structure. 2009;17:809-22 pubmed publisher
    ..In summary, our study reveals interaction types of SH3 domains, highlighting their great versatility. ..
  67. Jeong C. Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Growth of Gefitinib-resistant Non-small Cell Lung Cancer Cells by Inducing Apoptosis. J Cancer Prev. 2015;20:57-63 pubmed publisher
    ..Our study was aimed to investigate whether the inhibition of ubiquitin-specific peptidase 8 (USP8) could be an alternative strategy capable of overcoming acquired resistance to EGFR-TKIs for treatment of NSCLCs...
  68. Kaiser U. Cushing's disease: towards precision medicine. Cell Res. 2015;25:649-50 pubmed publisher
    The pathogenesis of Cushing's disease is poorly understood; two recent reports identifying somatic mutations in USP8 in pituitary corticotroph tumors provide exciting advances in this field...
  69. Ge C, Che L, Du C. The UBC Domain Is Required for BRUCE to Promote BRIT1/MCPH1 Function in DSB Signaling and Repair Post Formation of BRUCE-USP8-BRIT1 Complex. PLoS ONE. 2015;10:e0144957 pubmed publisher
    ..It acts as a scaffold to tether USP8 and BRIT1, together they form a nuclear BRUCE-USP8-BRIT1 complex, where BRUCE holds K63-ubiquitinated BRIT1 from ..
  70. Kaneko T, Kumasaka T, Ganbe T, Sato T, Miyazawa K, Kitamura N, et al. Structural insight into modest binding of a non-PXXP ligand to the signal transducing adaptor molecule-2 Src homology 3 domain. J Biol Chem. 2003;278:48162-8 pubmed
    ..adaptor molecule-2 (STAM2) SH3 domain in complex with a peptide with a novel motif derived from a ligand protein, UBPY. The derived KD value for this complex is 27 microM...
  71. Alwan H, van Leeuwen J. UBPY-mediated epidermal growth factor receptor (EGFR) de-ubiquitination promotes EGFR degradation. J Biol Chem. 2007;282:1658-69 pubmed
    ..The role of the de-ubiquitinating enzymes AMSH and UBPY in endosomal trafficking of cargo proteins such as the epidermal growth factor receptor (EGFR) has only very ..
  72. Ma Z, Song Z, Chen J, Wang Y, Li S, Zhou L, et al. Recurrent gain-of-function USP8 mutations in Cushing's disease. Cell Res. 2015;25:306-17 pubmed publisher
    ..ACTH-secreting PAs and matched blood samples, which revealed three types of somatic mutations in a candidate gene, USP8 (encoding ubiquitin-specific protease 8), exclusively in exon 14 in 8 of 12 ACTH-secreting PAs...
  73. Smith G, Fearnley G, Abdul Zani I, Wheatcroft S, Tomlinson D, Harrison M, et al. VEGFR2 Trafficking, Signaling and Proteolysis is Regulated by the Ubiquitin Isopeptidase USP8. Traffic. 2016;17:53-65 pubmed publisher
    ..In this study, the de-ubiquitinating enzyme, USP8, is shown to regulate VEGFR2 trafficking, de-ubiquitination, proteolysis and signal transduction...
  74. Ronchi C, Peverelli E, Herterich S, Weigand I, Mantovani G, Schwarzmayr T, et al. Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas. Eur J Endocrinol. 2016;174:363-72 pubmed publisher
    ..Somatic mutations at GNAS are causative in 30-40% of GH-secreting adenomas. Recently, mutations affecting the USP8 and PRKACA gene have been reported in ACTH-secreting pituitary adenomas and cortisol-secreting adrenocortical ..
  75. Uzilov A, Cheesman K, Fink M, Newman L, Pandya C, Lalazar Y, et al. Identification of a novel RASD1 somatic mutation in a USP8-mutated corticotroph adenoma. Cold Spring Harb Mol Case Stud. 2017;3:a001602 pubmed publisher
    ..In these tumors, somatic mutations in the gene USP8 have been identified as recurrent and pathogenic and are the sole known molecular driver for CD...
  76. Zhang Y, Yang K, Wang T, Li W, Jin X, Liu W. Nrdp1 Increases Ischemia Induced Primary Rat Cerebral Cortical Neurons and Pheochromocytoma Cells Apoptosis Via Downregulation of HIF-1? Protein. Front Cell Neurosci. 2017;11:293 pubmed publisher
    ..is accompanied by increased protein ubiquitylation and decreased protein levels of ubiquitin-specific protease 8 (USP8) in OGD-treated neurons, which led to a suppressed interaction between USP8 and HIF-1? and subsequently a reduction ..
  77. Wright M, Berlin I, Nash P. Regulation of endocytic sorting by ESCRT-DUB-mediated deubiquitination. Cell Biochem Biophys. 2011;60:39-46 pubmed publisher
    ..Two dubiquitinating enzymes--ubiquitin-specific protease 8 (USP8/Ubpy) and associated molecule with the SH3 domain of STAM (AMSH)--interact with ESCRT components to modulate the ..
  78. Novarino G, Fenstermaker A, Zaki M, Hofree M, Silhavy J, Heiberg A, et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014;343:506-511 pubmed publisher
    ..Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease...
  79. Durcan T, Tang M, Pérusse J, Dashti E, Aguileta M, McLelland G, et al. USP8 regulates mitophagy by removing K6-linked ubiquitin conjugates from parkin. EMBO J. 2014;33:2473-91 pubmed publisher
    ..We report here that USP8/UBPY, a deubiquitinating enzyme not previously implicated in mitochondrial quality control, is critical for parkin-..
  80. Hayashi K, Inoshita N, Kawaguchi K, Ibrahim Ardisasmita A, Suzuki H, Fukuhara N, et al. The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease. Eur J Endocrinol. 2016;174:213-26 pubmed publisher
    Somatic mutations in the ubiquitin-specific peptidase USP8 gene were recently detected in one- to two-third(s) of corticotroph adenomas of Cushing's disease (CD)...
  81. Pearson G, Chai B, Vozheiko T, Liu X, Kandarpa M, Piper R, et al. Clec16a, Nrdp1, and USP8 Form a Ubiquitin-Dependent Tripartite Complex That Regulates β-Cell Mitophagy. Diabetes. 2018;67:265-277 pubmed publisher
    ..for the assembly of a mitophagy regulatory complex, comprised of the E3 ligase Nrdp1, the deubiquitinase enzyme USP8, and Clec16a, a mediator of β-cell mitophagy with unclear function...
  82. Soares L, Seroogy C, Skrenta H, Anandasabapathy N, Lovelace P, Chung C, et al. Two isoforms of otubain 1 regulate T cell anergy via GRAIL. Nat Immunol. 2004;5:45-54 pubmed
    ..Thus, these two proteins have opposing epistatic functions in controlling the stability of GRAIL expression and the resultant anergy phenotype in T cells. ..
  83. 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
    ..Together, our findings elucidate deeply and extensively the mechanism of RNF8/RNF168 and USP11 to maintain the proper status of ubiquitylation γH2AX to repair DSB. ..
  84. Kim Y, Shiba Ishii A, Nakagawa T, Husni R, Sakashita S, Takeuchi T, et al. Ubiquitin-specific protease 8 is a novel prognostic marker in early-stage lung adenocarcinoma. Pathol Int. 2017;67:292-301 pubmed publisher
    ..Ubiquitin-specific protease 8 (USP8) has been reported to stabilize EGFR protein at the plasma membrane through the recycling pathway...
  85. Berlin I, Higginbotham K, Dise R, Sierra M, Nash P. The deubiquitinating enzyme USP8 promotes trafficking and degradation of the chemokine receptor 4 at the sorting endosome. J Biol Chem. 2010;285:37895-908 pubmed publisher
    ..Ubiquitin-specific protease 8 (USP8) has previously been implicated in endocytosis of several receptors by virtue of their deubiquitination...
  86. Oh Y, Lee S, Choi J, Suh H, Shim S, Song Y, et al. USP8 modulates ubiquitination of LRIG1 for Met degradation. Sci Rep. 2014;4:4980 pubmed publisher
    ..We also identified USP8 as a LRIG1-specific deubiquitinating enzyme, reporting the interaction between USP8 and LRIG1 for the first time...
  87. Faucz F, Tirosh A, Tatsi C, Berthon A, Hernández Ramírez L, Settas N, et al. Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease. J Clin Endocrinol Metab. 2017;102:2836-2843 pubmed publisher
    Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as the most common genetic alteration in patients with Cushing disease (CD)...
  88. Gnesutta N, Ceriani M, Innocenti M, Mauri I, Zippel R, Sturani E, et al. Cloning and characterization of mouse UBPy, a deubiquitinating enzyme that interacts with the ras guanine nucleotide exchange factor CDC25(Mm)/Ras-GRF1. J Biol Chem. 2001;276:39448-54 pubmed
    ..Therefore we called this new protein mouse UBPy (mUBPy)...
  89. Berruti G, Martegani E. The deubiquitinating enzyme mUBPy interacts with the sperm-specific molecular chaperone MSJ-1: the relation with the proteasome, acrosome, and centrosome in mouse male germ cells. Biol Reprod. 2005;72:14-21 pubmed
    The mouse USP8/mUBPy gene codifies a deubiquitinating enzyme expressed preferentially in testis and brain...
  90. Rigden D, Liu H, Hayes S, Urbé S, Clague M. Ab initio protein modelling reveals novel human MIT domains. FEBS Lett. 2009;583:872-8 pubmed publisher
    ..As a proof of principle, we have confirmed the novel MIT annotation for USP54 by in vitro profiling of binding to CHMP proteins. ..
  91. Hasdemir B, Murphy J, Cottrell G, Bunnett N. Endosomal deubiquitinating enzymes control ubiquitination and down-regulation of protease-activated receptor 2. J Biol Chem. 2009;284:28453-66 pubmed publisher
    ..occurs between early endosomes and lysosomes and involves the endosomal deubiquitinating proteases AMSH and UBPY. Expression of the catalytically inactive mutants, AMSH(D348A) and UBPY(C786S), caused an increase in PAR(2) ..