UBP41

Summary

Gene Symbol: UBP41
Description: ubiquitin specific peptidase 2
Alias: UBP41, USP9, ubiquitin carboxyl-terminal hydrolase 2, 41 kDa ubiquitin-specific protease, deubiquitinating enzyme 2, ubiquitin specific protease 12, ubiquitin specific protease 9, ubiquitin thioesterase 2, ubiquitin-specific-processing protease 2
Species: human
Products:     UBP41

Top Publications

  1. Nijman S, Luna Vargas M, Velds A, Brummelkamp T, Dirac A, Sixma T, et al. A genomic and functional inventory of deubiquitinating enzymes. Cell. 2005;123:773-86 pubmed
    ..In addition, we review the literature concerning these enzymes, with particular emphasis on their function, specificity, and the regulation of their activity. ..
  2. Allende Vega N, Sparks A, Lane D, Saville M. MdmX is a substrate for the deubiquitinating enzyme USP2a. Oncogene. 2010;29:432-41 pubmed publisher
    ..Knockdown of USP2a increases the sensitivity of NTERA-2 cells to cisplatin, raising the possibility that suppression of USP2a in combination with cisplatin may be an approach for cancer therapy. ..
  3. Oh K, Yang S, Park J, Seol J, Iemura S, Natsume T, et al. Control of AIF-mediated cell death by antagonistic functions of CHIP ubiquitin E3 ligase and USP2 deubiquitinating enzyme. Cell Death Differ. 2011;18:1326-36 pubmed publisher
    ..These findings indicate that CHIP and USP2 show antagonistic functions in the control of AIF-mediated cell death, and implicate the role of the enzymes as a switch for cells to live or die under stresses that cause tAIF release. ..
  4. Shi Y, Solomon L, Pereda Lopez A, Giranda V, Luo Y, Johnson E, et al. Ubiquitin-specific cysteine protease 2a (USP2a) regulates the stability of Aurora-A. J Biol Chem. 2011;286:38960-8 pubmed publisher
    ..USP2a interacts with Aurora-A directly in vitro and in vivo. In addition, Aurora-A is a substrate for USP2a in vitro and in vivo. Our study provides a novel mechanism for the role of USP2a in mediating the stability of Aurora-A. ..
  5. Graner E, Tang D, Rossi S, Baron A, Migita T, Weinstein L, et al. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell. 2004;5:253-61 pubmed
    ..Thus, the isopeptidase USP2a plays a critical role in prostate cancer cell survival through FAS stabilization and represents a therapeutic target in prostate cancer. ..
  6. Renatus M, Parrado S, D Arcy A, Eidhoff U, Gerhartz B, Hassiepen U, et al. Structural basis of ubiquitin recognition by the deubiquitinating protease USP2. Structure. 2006;14:1293-302 pubmed
    ..As several of those molecules are found at identical positions in the previously solved USP7/ubiquitin-aldehyde complex structure, we suggest a general mechanism of water-mediated ubiquitin recognition by USPs. ..
  7. Stevenson L, Sparks A, Allende Vega N, Xirodimas D, Lane D, Saville M. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. EMBO J. 2007;26:976-86 pubmed
    ..Our data identify the deubiquitinating enzyme USP2a as a novel regulator of the p53 pathway that acts through its ability to selectively target Mdm2. ..
  8. Shan J, Zhao W, Gu W. Suppression of cancer cell growth by promoting cyclin D1 degradation. Mol Cell. 2009;36:469-76 pubmed publisher
    ..These findings suggest that targeting USP2 is an effective approach to induce growth suppression in the cancer cells addicted to cyclin D1 expression. ..
  9. Kim J, Kim W, Liu Z, Loda M, Freeman M. The ubiquitin-specific protease USP2a enhances tumor progression by targeting cyclin A1 in bladder cancer. Cell Cycle. 2012;11:1123-30 pubmed publisher
    ..We conclude that USP2a impairs ubiquitination and stabilizes an important cell cycle regulator, cyclin A1, raising the possibility of USP2a targeting as a therapeutic strategy against bladder tumors in combination with chemotherapy. ..

More Information

Publications102 found, 100 shown here

  1. Mahul Mellier A, Datler C, Pazarentzos E, Lin B, Chaisaklert W, Abuali G, et al. De-ubiquitinating proteases USP2a and USP2c cause apoptosis by stabilising RIP1. Biochim Biophys Acta. 2012;1823:1353-65 pubmed publisher
    ..Hence, the ratio between USP2a and TRAF2 protein levels determines the cells' sensitivity to cell death. ..
  2. Liu Z, Zanata S, Kim J, Peterson M, Di Vizio D, Chirieac L, et al. The ubiquitin-specific protease USP2a prevents endocytosis-mediated EGFR degradation. Oncogene. 2013;32:1660-9 pubmed publisher
    ..Our findings suggest that regulation of deubiquitination could be exploited therapeutically in cancers overexpressing EGFR. ..
  3. Mahul Mellier A, Pazarentzos E, Datler C, Iwasawa R, Abuali G, Lin B, et al. De-ubiquitinating protease USP2a targets RIP1 and TRAF2 to mediate cell death by TNF. Cell Death Differ. 2012;19:891-9 pubmed publisher
    ..Consequently, downregulation of USP2a promotes NF-?B activation and protects cells against TNF-induced cell death. ..
  4. Tang H, Ding W, Ding Y, Wu J, Li Y. [Effects of Ubiquitination on the Expression of BCL6 Protein,Cell Proliferation and Apoptosis in K562/G01 Cells]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019;27:379-384 pubmed publisher
    ..05). ml364通过抑制usp2介导的bcl6蛋白去泛素化水平降低k562/g01细胞株bcl6 蛋白稳定性,使k562/g01细胞株中bcl6蛋白表达下调,从而增加耐药细胞对im的敏感性. ..
  5. Li Z, Tian S, Gu H, Wu Z, Nyagblordzro M, Feng G, et al. In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration. AAPS PharmSciTech. 2018;19:1882-1893 pubmed publisher
    ..The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development. ..
  6. Faresse N, Debonneville A, Staub O. USP2-45 represses aldosterone mediated responses by decreasing mineralocorticoid receptor availability. Cell Physiol Biochem. 2013;31:462-72 pubmed publisher
    ..This study provides a novel role for USP2-45 by playing a pivotal role in the regulation of the ubiquitylation state of MR and reveals the existence of a negative feedback loop for limiting the aldosterone induced response. ..
  7. Miura R, Araki A, Miyashita C, Kobayashi S, Kobayashi S, Wang S, et al. An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure: The Hokkaido study. Environ Int. 2018;115:21-28 pubmed publisher
    ..We suggest that prenatal exposure to PFASs may affect DNA methylation status at birth. Longitudinal studies are needed to examine whether methylation changes observed are associated with differential health outcomes. ..
  8. Moretti J, Chastagner P, Liang C, Cohn M, Israel A, Brou C. The ubiquitin-specific protease 12 (USP12) is a negative regulator of notch signaling acting on notch receptor trafficking toward degradation. J Biol Chem. 2012;287:29429-41 pubmed publisher
    ..These results characterize a new level of conserved regulation of Notch signaling by the ubiquitin system. ..
  9. He J, Lee H, Saha S, Ruan D, Guo H, Chan C. Inhibition of USP2 eliminates cancer stem cells and enhances TNBC responsiveness to chemotherapy. Cell Death Dis. 2019;10:285 pubmed publisher
    ..Our findings together demonstrate a previously unrecognized role of USP2 in mediating Twist activation and CSC enrichment, suggesting that targeting USP2 is a novel therapeutic strategy to tackle TNBC. ..
  10. Mao X, Luo W, Sun J, Yang N, Zhang L, Zhao Z, et al. Usp2-69 overexpression slows down the progression of rat anti-Thy1.1 nephritis. Exp Mol Pathol. 2016;101:249-258 pubmed publisher
    ..1 nephritis and, therefore, that exogenous plasmid injection via the renal artery enhanced by electrotransfer technology could be a promising avenue for glomerular disease research. ..
  11. Elhosseiny N, Amin M, Yassin A, Attia A. Acinetobacter baumannii universal stress protein A plays a pivotal role in stress response and is essential for pneumonia and sepsis pathogenesis. Int J Med Microbiol. 2015;305:114-23 pubmed publisher
    ..Our study highlights the role of UspA as an important contributor to the A. baumannii stress and virulence machineries, and polishes it as a plausible target for new therapeutics. ..
  12. Narayanan N, Wang Z, Li L, Yang Y. Arginine methylation of USP9X promotes its interaction with TDRD3 and its anti-apoptotic activities in breast cancer cells. Cell Discov. 2017;3:16048 pubmed publisher
    ..This study provides a novel candidate strategy for targeting apoptosis pathways in cancer therapy. ..
  13. Molusky M, Li S, Ma D, Yu L, Lin J. Ubiquitin-specific protease 2 regulates hepatic gluconeogenesis and diurnal glucose metabolism through 11β-hydroxysteroid dehydrogenase 1. Diabetes. 2012;61:1025-35 pubmed publisher
    ..Together, these studies delineate a novel pathway that links hormonal and circadian signals to gluconeogenesis and glucose homeostasis. ..
  14. Qu Q, Mao Y, Xiao G, Fei X, Wang J, Zhang Y, et al. USP2 promotes cell migration and invasion in triple negative breast cancer cell lines. Tumour Biol. 2015;36:5415-23 pubmed publisher
    ..The present study showed that USP2 expression is associated with TNBC cell line's invasiveness and poor survival of breast cancer patients and may serve as a prognostic biomarker and therapeutic target for TNBC. ..
  15. Zhou H, Wertz I, O Rourke K, Ultsch M, Seshagiri S, Eby M, et al. Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO. Nature. 2004;427:167-71 pubmed
    ..Thus, the adaptor protein Bcl10 promotes activation of NF-kappaB transcription factors through paracaspase- and UBC13-dependent ubiquitination of NEMO. ..
  16. Shirakawa J, Harada H, Noda M, Ezura Y. PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression. Calcif Tissue Int. 2016;98:306-15 pubmed publisher
    ..Our data indicate that Usp2 is required for the PTH1-34-induced proliferation of osteoblasts. ..
  17. Pouly D, Chenaux S, Martin V, Babis M, Koch R, Nagoshi E, et al. USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level. PLoS ONE. 2016;11:e0145155 pubmed publisher
    ..Taken together these data prompt us to define USP2-45 as the first clock output effector acting at the post-translational level at cell membranes and possibly regulating membrane permeability of Ca2+. ..
  18. Akhtar N, Singh A, Ahmed S. MicroRNA-17 Suppresses TNF-? Signaling by Interfering with TRAF2 and cIAP2 Association in Rheumatoid Arthritis Synovial Fibroblasts. J Immunol. 2016;197:2219-28 pubmed publisher
    ..In conclusion, this study provides evidence for the role of miR-17 as a negative regulator of TNF-? signaling by modulating the protein ubiquitin processes in RA SFs. ..
  19. Hribar M, Trontelj J, Klančar U, Markun B, Čeligoj Dujc T, Legen I. A Novel Intestine Model Apparatus for Drug Dissolution Capable of Simulating the Peristaltic Action. AAPS PharmSciTech. 2017;18:1646-1656 pubmed publisher
    ..In conclusion, the model parameters were efficiently controlled to ensure the dissolution conditions crucial for evaluating the in vivo release performance of the tested formulations. ..
  20. Guiastrennec B, Söderlind E, Richardson S, Peric A, Bergstrand M. In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status. Pharm Res. 2017;34:847-859 pubmed publisher
    ..99 rpm). The in silico model accurately predicted the erosion profiles of HPMC matrix tablets under fasting and postprandial status and can be used to facilitate future development of extended release tablets. ..
  21. Jeong P, Ha Y, Yun S, Yoon H, Freeman M, Kim J, et al. Assess the expression of ubiquitin specific protease USP2a for bladder cancer diagnosis. BMC Urol. 2015;15:80 pubmed publisher
    ..024), but not in NMIBC patients. Our findings suggest that USP2a mRNA may be considered as a diagnostic marker candidate for bladder cancer, in particular, to stratify MIBC patients with a more invasive phenotype. ..
  22. Tang L, Li Y, Liu Y, Wang J, Liu D, Tian Q. USP12 regulates cell cycle progression by involving c-Myc, cyclin D2 and BMI-1. Gene. 2016;578:92-9 pubmed publisher
    ..The effect of USP12 on HeLa cell apoptosis was not observed in our study. These results suggest that USP12 may be responsible for HeLa cell growth by affecting cell cycle progression. ..
  23. Mercuri A, Pagliari M, Baxevanis F, Fares R, Fotaki N. Understanding and predicting the impact of critical dissolution variables for nifedipine immediate release capsules by multivariate data analysis. Int J Pharm. 2017;518:41-49 pubmed publisher
    ..The multivariate analysis revealed that the concentration of ethanol used in the in vitro dissolution experiments (47% v/v) can be lowered to less than 20% v/v, reflecting recently found physiological conditions. ..
  24. Yang H, Seo S, Shin S, Min S, Kang M, Yoo R, et al. 3,3'-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity. Mol Nutr Food Res. 2017;61: pubmed publisher
    ..Our findings indicate that cruciferous vegetables, which can produce DIM as a metabolite, have the potential to prevent or treat chronic obesity. ..
  25. Chuang S, Cheng S, Tang H, Sun C, Chou C. 6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2. Sci Rep. 2018;8:3102 pubmed publisher
    ..Our study provides a clear rationale for the clinical evaluation of 6-thioguanine for USP2-upregulated cancers. ..
  26. Sun Y, Qin Z, Li Q, Wan J, Cheng M, Wang P, et al. MicroRNA-124 negatively regulates LPS-induced TNF-α production in mouse macrophages by decreasing protein stability. Acta Pharmacol Sin. 2016;37:889-97 pubmed publisher
    ..miR-124, targeting USP2 and USP14, negatively regulates LPS-induced TNF-α production in mouse macrophages, suggesting miR-124 as a new therapeutic target in inflammation-related diseases. ..
  27. Ginster S, Bardet M, Unterreiner A, Malinverni C, Renner F, Lam S, et al. Two Antagonistic MALT1 Auto-Cleavage Mechanisms Reveal a Role for TRAF6 to Unleash MALT1 Activation. PLoS ONE. 2017;12:e0169026 pubmed publisher
    ..Altogether, this study provides further insights into mechanisms that regulate the scaffolding and activation cycle of MALT1. It also emphasizes the reduced functional capacity of MALT1B as compared to MALT1A. ..
  28. Li C, Zhang J, Xu H, Chang M, Lv C, Xue W, et al. Retigabine ameliorates acute stress-induced impairment of spatial memory retrieval through regulating USP2 signaling pathways in hippocampal CA1 area. Neuropharmacology. 2018;135:151-162 pubmed publisher
    ..Our results have identified USP2 as a key molecule that mediates stress-induced spatial memory retrieval impairment, which provides a framework for new druggable targets to conceptually treat stress-associated cognitive deficits. ..
  29. Ruffieux Daidié D, Poirot O, Boulkroun S, Verrey F, Kellenberger S, Staub O. Deubiquitylation regulates activation and proteolytic cleavage of ENaC. J Am Soc Nephrol. 2008;19:2170-80 pubmed publisher
    ..In summary, these data suggest that Usp2-45 deubiquitylation of ENaC enhances the proteolytic activation of both alphaENaC and gammaENaC, possibly by inducing a conformational change and by interfering with endocytosis, respectively. ..
  30. Kosinsky R, Wegwitz F, Hellbach N, Dobbelstein M, Mansouri A, Vogel T, et al. Usp22 deficiency impairs intestinal epithelial lineage specification in vivo. Oncotarget. 2015;6:37906-18 pubmed publisher
    ..Taken together, we provide evidence for a physiological role for USP22 in controlling cell differentiation and lineage specification. ..
  31. McClurg U, Harle V, Nabbi A, Batalha Pereira A, Walker S, Coffey K, et al. Ubiquitin-specific protease 12 interacting partners Uaf-1 and WDR20 are potential therapeutic targets in prostate cancer. Oncotarget. 2015;6:37724-36 pubmed publisher
  32. Scheubel E, Lindenberg M, Beyssac E, Cardot J. Small Volume Dissolution Testing as a Powerful Method during Pharmaceutical Development. Pharmaceutics. 2010;2:351-363 pubmed
    ..In this regard, small volume dissolution is a method of choice in case of screening for critical quality attributes of rapidly dissolving tablets, where it is often difficult to detect differences using standard working conditions. ..
  33. Shin Y, Chen J, Chang S. The molecular determinants for distinguishing between ubiquitin and NEDD8 by USP2. Sci Rep. 2017;7:2304 pubmed publisher
    ..The same results were also discovered when Ub, Ub4K/12E/14E/72A, NEDD8, and NEDD84F/12T/14T/72R were incubated with USP21. ..
  34. Castañeda C, Dixon E, Walker O, Chaturvedi A, Nakasone M, Curtis J, et al. Linkage via K27 Bestows Ubiquitin Chains with Unique Properties among Polyubiquitins. Structure. 2016;24:423-36 pubmed publisher
    ..Binding studies and mutagenesis confirmed this prediction, further highlighting structural/recognition versatility of polyubiquitins and the potential power of determining function from elucidation of conformational ensembles. ..
  35. Zhang M, Zhang M, Zhang Q, Zhu G, Yuan L, Zhang D, et al. USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA. Cell Res. 2016;26:1302-1319 pubmed publisher
    ..Our findings thus uncover previously uncharacterized roles of USP18 and USP20 in mediating virus-triggered signaling and contribute to the understanding of the complicated regulatory system of the innate antiviral responses. ..
  36. Gopinath P, Mahammed A, Ohayon S, Gross Z, Brik A. Understanding and predicting the potency of ROS-based enzyme inhibitors, exemplified by naphthoquinones and ubiquitin specific protease-2. Chem Sci. 2016;7:7079-7086 pubmed publisher
  37. Mashtalir N, Daou S, Barbour H, Sen N, Gagnon J, Hammond Martel I, et al. Autodeubiquitination protects the tumor suppressor BAP1 from cytoplasmic sequestration mediated by the atypical ubiquitin ligase UBE2O. Mol Cell. 2014;54:392-406 pubmed publisher
    ..Thus, UBE2O defines an atypical ubiquitin-signaling pathway that coordinates the function of BAP1 and establishes a paradigm for regulation of nuclear trafficking of chromatin-associated proteins. ..
  38. Rougier J, Albesa M, Syam N, Halet G, Abriel H, Viard P. Ubiquitin-specific protease USP2-45 acts as a molecular switch to promote α2δ-1-induced downregulation of Cav1.2 channels. Pflugers Arch. 2015;467:1919-29 pubmed publisher
    ..These results suggest that USP2-45 binding to α2δ-1 promotes the de-ubiquitylation of both Cav1.2 and α2δ-1 subunits, in order to regulate the expression of Cav1.2 channels at the plasma membrane. ..
  39. Durcan T, Kontogiannea M, Thorarinsdottir T, Fallon L, WILLIAMS A, Djarmati A, et al. The Machado-Joseph disease-associated mutant form of ataxin-3 regulates parkin ubiquitination and stability. Hum Mol Genet. 2011;20:141-54 pubmed publisher
  40. Goncu E, Uranlı R, Selek G, Parlak O. Developmental Expression of Ecdysone-Related Genes Associated With Metamorphic Changes During Midgut Remodeling of Silkworm Bombyx mori (Lepidoptera:Bombycidae). J Insect Sci. 2016;16: pubmed publisher
    ..All of these results showed the determination the cell fate in Bombyx mori (Linnaeus) midgut depends on type of ecdysone receptor isoforms and ecdysone-related transcription factors. ..
  41. Metzig M, Nickles D, Falschlehner C, Lehmann Koch J, Straub B, Roth W, et al. An RNAi screen identifies USP2 as a factor required for TNF-?-induced NF-?B signaling. Int J Cancer. 2011;129:607-18 pubmed publisher
    ..Together, our results implicate USP2 as a novel positive regulator of TNF-?-induced NF-?B signaling and show that its expression is altered in tumor cells. ..
  42. Wing S. Deubiquitinases in skeletal muscle atrophy. Int J Biochem Cell Biol. 2013;45:2130-5 pubmed publisher
    ..This article is part of a Directed Issue entitled: Molecular basis of muscle wasting. ..
  43. Mercuri A, Fares R, Bresciani M, Fotaki N. An in vitro-in vivo correlation study for nifedipine immediate release capsules administered with water, alcoholic and non-alcoholic beverages: Impact of in vitro dissolution media and hydrodynamics. Int J Pharm. 2016;499:330-342 pubmed publisher
    ..This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages. ..
  44. Krzystanek K, Rasmussen H, Grunnet M, Staub O, Olesen S, Abriel H, et al. Deubiquitylating enzyme USP2 counteracts Nedd4-2-mediated downregulation of KCNQ1 potassium channels. Heart Rhythm. 2012;9:440-8 pubmed publisher
    ..These results demonstrate that USP2 can be a potent regulator of KCNQ1 surface density. USP2, which is well expressed in many tissues, may therefore be important in controlling the KCNQ1 channel dynamics in vivo. ..
  45. Saha S, Caviness G, Yi G, Raymond E, Mbow M, Kao C. E3 Ubiquitin Ligase RNF125 Activates Interleukin-36 Receptor Signaling and Contributes to Its Turnover. J Innate Immun. 2018;10:56-69 pubmed publisher
    ..These results demonstrate that RNF125 has multiple regulatory roles in the signaling, trafficking, and turnover of the IL-36R. ..
  46. Gousseva N, Baker R. Gene structure, alternate splicing, tissue distribution, cellular localization, and developmental expression pattern of mouse deubiquitinating enzyme isoforms Usp2-45 and Usp2-69. Gene Expr. 2003;11:163-79 pubmed
    ..We can find no evidence for a reported 41-kDa isoform (UBP41) in any sequence databases. Usp2-69 is able to form a complex with Usp2-45 and with itself...
  47. González Prieto R, Cuijpers S, Kumar R, Hendriks I, Vertegaal A. c-Myc is targeted to the proteasome for degradation in a SUMOylation-dependent manner, regulated by PIAS1, SENP7 and RNF4. Cell Cycle. 2015;14:1859-72 pubmed publisher
    ..Our results provide novel insight into the complexity of c-Myc post-translational regulation. ..
  48. Braunstein I, Zach L, Allan S, Kalies K, Stanhill A. Proteasomal degradation of preemptive quality control (pQC) substrates is mediated by an AIRAPL-p97 complex. Mol Biol Cell. 2015;26:3719-27 pubmed publisher
    ..We also demonstrate p97's role in pQC processing of preproinsulin in cases of naturally occurring mutations within the signal sequence of insulin. ..
  49. Wei T, Folkersen L, Biskup E, Xu N, Manfé V, Niazi O, et al. Ubiquitin-specific peptidase 2 as a potential link between microRNA-125b and psoriasis. Br J Dermatol. 2017;176:723-731 pubmed publisher
    ..Findings, such as the ones presented herein, are therefore necessary in order to achieve the future of personalized medicine. ..
  50. Wang T, Huang M, Lin H, Hsiang C, Ko A, Chang W, et al. UCP2 A55V variant is associated with obesity and related phenotypes in an aboriginal community in Taiwan. Int J Obes (Lond). 2007;31:1746-52 pubmed
    ..5% of obese disorders and increase insulin concentrations. The V-A-T haplotype within UCP2-UCP3 gene cluster is also significantly associated with obesity in Paiwan aborigines. ..
  51. Tao B, He H, Shi X, Wang C, Li W, Li B, et al. Up-regulation of USP2a and FASN in gliomas correlates strongly with glioma grade. J Clin Neurosci. 2013;20:717-20 pubmed publisher
    ..These findings expand our understanding of the molecular profiling of glioma and could shed light on new diagnostic criteria for gliomas. ..
  52. Krutauz D, Reis N, Nakasone M, Siman P, Zhang D, Kirkpatrick D, et al. Extended ubiquitin species are protein-based DUB inhibitors. Nat Chem Biol. 2014;10:664-70 pubmed publisher
  53. 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. ..
  54. Naik E, Dixit V. Usp9X Is Required for Lymphocyte Activation and Homeostasis through Its Control of ZAP70 Ubiquitination and PKCβ Kinase Activity. J Immunol. 2016;196:3438-51 pubmed publisher
    ..The pleiotropic effect of Usp9X during Ag-receptor signaling highlights its importance for the development of an effective and durable adaptive immune response. ..
  55. Wang Z, Xie W, Zhu M, Zhou H. Development of a highly reliable assay for ubiquitin-specific protease 2 inhibitors. Bioorg Med Chem Lett. 2017;27:4015-4018 pubmed publisher
    ..A number of effective USP2 inhibitors were also identified using this assay. ..
  56. Kitamura H, Ishino T, Shimamoto Y, Okabe J, Miyamoto T, Takahashi E, et al. Ubiquitin-Specific Protease 2 Modulates the Lipopolysaccharide-Elicited Expression of Proinflammatory Cytokines in Macrophage-like HL-60 Cells. Mediators Inflamm. 2017;2017:6909415 pubmed publisher
    ..In summary, USP2 modulates proinflammatory cytokine induction, possibly through modification of Oct proteins, in macrophages following TLR4 activation. ..
  57. Baek S, Choi K, Yoo Y, Cho J, Baker R, Tanaka K, et al. Molecular cloning of a novel ubiquitin-specific protease, UBP41, with isopeptidase activity in chick skeletal muscle. J Biol Chem. 1997;272:25560-5 pubmed
    A cDNA encoding a new ubiquitin-specific protease, UBP41, in chick skeletal muscle was cloned using an Escherichia coli-based in vivo screening method...
  58. Bozza W, Liang Q, Gong P, Zhuang Z. Transient kinetic analysis of USP2-catalyzed deubiquitination reveals a conformational rearrangement in the K48-linked diubiquitin substrate. Biochemistry. 2012;51:10075-86 pubmed publisher
    ..Our results provide useful insights into the mechanism of how USP recognizes ubiquitin moieties in a chain structure, which is important for understanding USP catalysis and developing inhibitors against USPs. ..
  59. Louis M, Hofmann K, Broemer M. Evolutionary Loss of Activity in De-Ubiquitylating Enzymes of the OTU Family. PLoS ONE. 2015;10:e0143227 pubmed publisher
    ..Using an in vivo RNAi approach, we show that CG3251 might function in the regulation of Inhibitor of Apoptosis (IAP)-antagonist-induced apoptosis, presumably in a DUB-independent manner. ..
  60. Nelson J, Sorrentino V, Avagliano Trezza R, Heride C, Urbé S, Distel B, et al. The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL. Circ Res. 2016;118:410-9 pubmed publisher
    ..Our findings identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL. ..
  61. Wang S, Wu H, Liu Y, Sun J, Zhao Z, Chen Q, et al. Expression of USP2-69 in mesangial cells in vivo and in vitro. Pathol Int. 2010;60:184-92 pubmed publisher
    ..These findings suggest that USP2-69 was upregulated in mesangial cells during mesangial proliferative glomerulonephritides in vivo and in vitro, which may relate to the proliferation of mesangial cells. ..
  62. Benassi B, Marani M, Loda M, Blandino G. USP2a alters chemotherapeutic response by modulating redox. Cell Death Dis. 2013;4:e812 pubmed publisher
    ..In light of these findings, targeting Myc and/or miR-34b/c might revert chemo-resistance. ..
  63. Zeman M, Lin J, Freire R, Cimprich K. DNA damage-specific deubiquitination regulates Rad18 functions to suppress mutagenesis. J Cell Biol. 2014;206:183-97 pubmed publisher
  64. Mizutani N, Inoue M, Omori Y, Ito H, Tamiya Koizumi K, Takagi A, et al. Increased acid ceramidase expression depends on upregulation of androgen-dependent deubiquitinases, USP2, in a human prostate cancer cell line, LNCaP. J Biochem. 2015;158:309-19 pubmed publisher
    ..Thus, ACDase regulation by androgen in androgen-sensitive LNCaP cells is mainly due to its prolonged protein half-life by androgen-stimulated USP2 expression. ..
  65. Reglinski K, Keil M, Altendorf S, Waithe D, Eggeling C, Schliebs W, et al. Peroxisomal Import Reduces the Proapoptotic Activity of Deubiquitinating Enzyme USP2. PLoS ONE. 2015;10:e0140685 pubmed publisher
  66. Wang T, Evdokimov E, Yiadom K, Yan Z, Chock P, Yang D. Biotin-ubiquitin tagging of mammalian proteins in Escherichia coli. Protein Expr Purif. 2003;30:140-9 pubmed
    ..Additionally, the ubiquitin protein hydrolase UBP41, expressed and purified as biotin-UBP41, efficiently and specifically cleaved off the biotin-ubiquitin tag from ..
  67. Liu H, Buus R, Clague M, Urbé S. Regulation of ErbB2 receptor status by the proteasomal DUB POH1. PLoS ONE. 2009;4:e5544 pubmed publisher
    ..We propose that POH1 may deubiquitinate ErbB2 and that this activity is not necessarily coupled to proteasomal degradation. ..
  68. Mullen J, Chen C, Brill S. Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase. Mol Cell Biol. 2010;30:3737-48 pubmed publisher
    ..The results suggest that Wss1 is a SUMO-dependent isopeptidase that acts on sumoylated substrates as they undergo proteasomal degradation. ..
  69. Bremm A, Freund S, Komander D. Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne. Nat Struct Mol Biol. 2010;17:939-47 pubmed publisher
    ..Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications. ..
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    ..Furthermore, USP2a deSUMOylated TRAF6. Our findings implicate that USP2a plays an important role in TCR signaling by deSUMOylating TRAF6 and mediating TRAF6-MALT1 interaction. ..
  71. Takeda A, Oberoi Khanuja T, Glatz G, Schulenburg K, Scholz R, Carpy A, et al. Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1. EMBO J. 2014;33:1784-801 pubmed publisher
    ..Our results reveal a novel, obligatory role for IAPs and ubiquitination in the physical and functional disassembly of ERK5-MAPK module and human muscle cell differentiation. ..
  72. Zhang L, Zhao X, Zhang M, Zhao W, Gao C. Ubiquitin-specific protease 2b negatively regulates IFN-? production and antiviral activity by targeting TANK-binding kinase 1. J Immunol. 2014;193:2230-7 pubmed publisher
    ..Therefore, our findings demonstrated that USP2b deubiquitinates K63-linked polyubiquitin chains from TBK1 to terminate TBK1 activation and negatively regulate IFN-? signaling and antiviral immune response. ..
  73. Davis M, Pragani R, Fox J, Shen M, Parmar K, Gaudiano E, et al. Small Molecule Inhibition of the Ubiquitin-specific Protease USP2 Accelerates cyclin D1 Degradation and Leads to Cell Cycle Arrest in Colorectal Cancer and Mantle Cell Lymphoma Models. J Biol Chem. 2016;291:24628-24640 pubmed
    ..These effects by a small molecule inhibitor support a key role for USP2 as a regulator of cell cycle, DNA repair, and tumor cell growth. ..
  74. Gewies A, Grimm S. UBP41 is a proapoptotic ubiquitin-specific protease. Cancer Res. 2003;63:682-8 pubmed
    We have isolated Ubp41, a ubiquitin-specific protease, in a screen for proapoptoticgenes. We found that overexpression of Ubp41 is sufficient to elicit all features of apoptosis in human cells...
  75. Yang Y, Hou J, Qu L, Wang G, Ju H, Zhao Z, et al. [Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2007;23:504-6 pubmed
    ..The differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues was investigated...
  76. He X, Li Y, Li C, Liu L, Zhang X, Liu Y, et al. USP2a negatively regulates IL-1?- and virus-induced NF-?B activation by deubiquitinating TRAF6. J Mol Cell Biol. 2013;5:39-47 pubmed publisher
    ..Because of the importance of TRAF6 in multiple pathways leading to NF-?B activation, these findings provide a general regulatory mechanism for NF-?B activation triggered by different stimuli. ..
  77. Tong X, Buelow K, Guha A, Rausch R, Yin L. USP2a protein deubiquitinates and stabilizes the circadian protein CRY1 in response to inflammatory signals. J Biol Chem. 2012;287:25280-91 pubmed publisher
    ..Therefore, USP2a potentially mediates circadian disruption by suppressing the CRY1 degradation during inflammation...
  78. Morita M, Ler L, Fabian M, Siddiqui N, Mullin M, Henderson V, et al. A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development. Mol Cell Biol. 2012;32:3585-93 pubmed publisher
    ..We propose a model by which the m4EHP-GIGYF2 complex represses translation of a subset of mRNAs during embryonic development, as was previously reported for d4EHP. ..
  79. 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
    ..We speculate that the ability to induce homologous recombination in G1 cells with defined factors could spur the development of gene-targeting applications in non-dividing cells. ..
  80. Wei T, Biskup E, Gjerdrum L, Niazi O, Ødum N, Gniadecki R. Ubiquitin-specific protease 2 decreases p53-dependent apoptosis in cutaneous T-cell lymphoma. Oncotarget. 2016;7:48391-48400 pubmed publisher
    ..Taken together, our findings suggest that USP2 stabilizes Mdm2 which antagonizes pro-apoptotic activity of p53 and possibly contributes to therapeutic resistance in CTCL. ..
  81. Leung I, Dekel A, Shifman J, Sidhu S. Saturation scanning of ubiquitin variants reveals a common hot spot for binding to USP2 and USP21. Proc Natl Acad Sci U S A. 2016;113:8705-10 pubmed publisher
    ..The Ubv core functional epitope contacts residues that are conserved in the human USP family, and thus it is likely important for the interactions of Ub across many family members. ..
  82. Erickson Johnson M, Chou M, Evers B, Roth C, Seys A, Jin L, et al. Nodular fasciitis: a novel model of transient neoplasia induced by MYH9-USP6 gene fusion. Lab Invest. 2011;91:1427-33 pubmed publisher
    ..Considering the self-limited nature of the lesion, NF may represent a model of 'transient neoplasia', as it is, to our knowledge, the first example of a self-limited human disease characterized by a recurrent somatic gene fusion event. ..
  83. Nepal S, Shrestha A, Park P. Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells. Mol Cell Endocrinol. 2015;412:44-55 pubmed publisher
    ..Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines. ..
  84. Ren Y, Zhao P, Liu J, Yuan Y, Cheng Q, Zuo Y, et al. Deubiquitinase USP2a Sustains Interferons Antiviral Activity by Restricting Ubiquitination of Activated STAT1 in the Nucleus. PLoS Pathog. 2016;12:e1005764 pubmed publisher
    ..These findings uncover a positive mechanism by which IFNs execute efficient antiviral signaling and function, and may provide potential targets for improving IFNs-based antiviral therapy. ..
  85. Oberfeld B, Ruffieux Daidié D, Vitagliano J, Pos K, Verrey F, Staub O. Ubiquitin-specific protease 2-45 (Usp2-45) binds to epithelial Na+ channel (ENaC)-ubiquitylating enzyme Nedd4-2. Am J Physiol Renal Physiol. 2011;301:F189-96 pubmed publisher
    ..Taken together, the data support the conclusion that Usp2-45 action on ENaC is promoted by various interactions, including through binding to Nedd4-2 that is suggested to position Usp2-45 favorably for ENaC deubiquitylation. ..
  86. Masuda Y, Suzuki M, Kawai H, Hishiki A, Hashimoto H, Masutani C, et al. En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs. Nucleic Acids Res. 2012;40:10394-407 pubmed publisher
    ..The resultant Ub chain is subsequently transferred to PCNA by RAD18. Thus, template switching may be promoted under certain circumstances in which both RAD18 and HLTF are coordinately recruited to sites of stalled replication. ..
  87. 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. ..
  88. Wang C, Wang J, Liu Z, Ma X, Wang X, Jin H, et al. Ubiquitin-specific protease 2a stabilizes MDM4 and facilitates the p53-mediated intrinsic apoptotic pathway in glioblastoma. Carcinogenesis. 2014;35:1500-9 pubmed publisher
    ..This apoptotic response was reduced by knockdown of p53 but not p21. Our results suggest that USP2a binds to and stabilizes MDM4; thus in turn, it enhances the mitochondrial localization of p53 and promotes apoptosis in glioma cells. ..
  89. Smith N, Adle D, Zhao M, Qin X, Kim H, Lee J. Endoplasmic Reticulum-associated Degradation of Pca1p, a Polytopic Protein, via Interaction with the Proteasome at the Membrane. J Biol Chem. 2016;291:15082-92 pubmed publisher
    ..These results indicate that extraction and degradation of polytopic membrane proteins at the ER is a coupled event. This mechanism would relieve the cost of exposed hydrophobic domains in the cytosol during ERAD. ..
  90. Köglsberger S, Cordero Maldonado M, Antony P, Forster J, Garcia P, Buttini M, et al. Gender-Specific Expression of Ubiquitin-Specific Peptidase 9 Modulates Tau Expression and Phosphorylation: Possible Implications for Tauopathies. Mol Neurobiol. 2017;54:7979-7993 pubmed publisher
    ..We identify the sex-linked ubiquitin-specific peptidase 9 (USP9) as an outstanding candidate gene with highly significant expression differences between the genders and male-..
  91. Zhu H, Gao F. The Molecular Mechanisms of Regulation on USP2's Alternative Splicing and the Significance of Its Products. Int J Biol Sci. 2017;13:1489-1496 pubmed publisher
    ..In general, we collect and summarize the factors involved in the alternative splicing of USP2 in this review to further understand the mechanism behind the USP2's alternative splicing...
  92. 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. ..