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Published in: Breast Cancer Research 5/2014

Open Access 01-10-2014 | Review

Ubiquitin-specific proteases as therapeutic targets for the treatment of breast cancer

Authors: Anupama Pal, Nicholas J Donato

Published in: Breast Cancer Research | Issue 5/2014

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Abstract

Key mediators of signaling pathways in breast cancer involve post-translational protein modification, primarily mediated through phosphorylation and ubiquitination. While previous studies focused on phosphorylation events, more recent analysis suggests that ubiquitin plays a parallel and equally important role in several signaling and cell regulatory events in breast cancer. Availability of new tools capable of sensitive detection of gene mutations and aberrant expression of genes and proteins coupled with gene-specific knockdown and silencing protocols have provided insight into the previously unexplored ubiquitin regulatory process within these tumors. Ubiquitin-specific proteases are one class of enzymes with protein deubiquitinating activity, making up the majority of protein deubiquitinating diversity within mammalian cells. Ubiquitin-specific proteases are also emerging as potential therapeutic targets in many diseases, including cancer. In this report, we summarize the involvement of this class of enzymes in breast cancer signaling and cell regulation and illustrate the potential for additional studies to define novel targets and approaches in breast cancer therapy.
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Literature
1.
go back to reference Hershko A, Ciechanover A: The ubiquitin system. Annu Rev Biochem. 1998, 67: 425-479. 10.1146/annurev.biochem.67.1.425.CrossRefPubMed Hershko A, Ciechanover A: The ubiquitin system. Annu Rev Biochem. 1998, 67: 425-479. 10.1146/annurev.biochem.67.1.425.CrossRefPubMed
2.
go back to reference Glickman MH, Ciechanover A: The ubiquitin–proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002, 82: 373-428.CrossRefPubMed Glickman MH, Ciechanover A: The ubiquitin–proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002, 82: 373-428.CrossRefPubMed
3.
go back to reference Shi D, Grossman SR: Ubiquitin becomes ubiquitous in cancer: emerging roles of ubiquitin ligases and deubiquitinases in tumorigenesis and as therapeutic targets. Cancer Biol Ther. 2010, 10: 737-747. 10.4161/cbt.10.8.13417.CrossRefPubMedPubMedCentral Shi D, Grossman SR: Ubiquitin becomes ubiquitous in cancer: emerging roles of ubiquitin ligases and deubiquitinases in tumorigenesis and as therapeutic targets. Cancer Biol Ther. 2010, 10: 737-747. 10.4161/cbt.10.8.13417.CrossRefPubMedPubMedCentral
4.
go back to reference Dennissen FJA, Kholod N, van Leeuwen FW: The ubiquitin proteasome system in neurodegenerative diseases: culprit, accomplice or victim?. Prog Neurobiol. 2012, 96: 190-207. 10.1016/j.pneurobio.2012.01.003.CrossRefPubMed Dennissen FJA, Kholod N, van Leeuwen FW: The ubiquitin proteasome system in neurodegenerative diseases: culprit, accomplice or victim?. Prog Neurobiol. 2012, 96: 190-207. 10.1016/j.pneurobio.2012.01.003.CrossRefPubMed
5.
go back to reference Yang Y, Kitagaki J, Dai RM, Tsai YC, Lorick KL, Ludwig RL, Pierre SA, Jensen JP, Davydov IV, Oberoi P, Li CC, Kenten JH, Beutler JA, Vousden KH, Weissman AM: Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007, 67: 9472-9481. 10.1158/0008-5472.CAN-07-0568.CrossRefPubMed Yang Y, Kitagaki J, Dai RM, Tsai YC, Lorick KL, Ludwig RL, Pierre SA, Jensen JP, Davydov IV, Oberoi P, Li CC, Kenten JH, Beutler JA, Vousden KH, Weissman AM: Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007, 67: 9472-9481. 10.1158/0008-5472.CAN-07-0568.CrossRefPubMed
6.
go back to reference Xu GW, Ali M, Wood TE, Wong D, Maclean N, Wang X, Gronda M, Skrtic M, Li X, Hurren R, Mao X, Venkatesan M, Beheshti Zavareh R, Ketela T, Reed JC, Rose D, Moffat J, Batey RA, Dhe-Paganon S, Schimmer AD: The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. Blood. 2010, 115: 2251-2259. 10.1182/blood-2009-07-231191.CrossRefPubMedPubMedCentral Xu GW, Ali M, Wood TE, Wong D, Maclean N, Wang X, Gronda M, Skrtic M, Li X, Hurren R, Mao X, Venkatesan M, Beheshti Zavareh R, Ketela T, Reed JC, Rose D, Moffat J, Batey RA, Dhe-Paganon S, Schimmer AD: The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. Blood. 2010, 115: 2251-2259. 10.1182/blood-2009-07-231191.CrossRefPubMedPubMedCentral
7.
go back to reference Zou Q, Jin J, Hu H, Li HS, Romano S, Xiao Y, Nakaya M, Zhou X, Cheng X, Yang P, Lozano G, Zhu C, Watowich SS, Ullrich SE, Sun SC: USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses. Nat Immunol. 2014, 15: 562-570. 10.1038/ni.2885.CrossRefPubMedPubMedCentral Zou Q, Jin J, Hu H, Li HS, Romano S, Xiao Y, Nakaya M, Zhou X, Cheng X, Yang P, Lozano G, Zhu C, Watowich SS, Ullrich SE, Sun SC: USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses. Nat Immunol. 2014, 15: 562-570. 10.1038/ni.2885.CrossRefPubMedPubMedCentral
8.
go back to reference Zhang Z, Chu XJ, Liu JJ, Ding Q, Zhang J, Bartkovitz D, Jiang N, Karnachi P, So SS, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassiley L, Graves B: Discovery of potent and orally active p53-MDM2 inhibitors RO5353 and RO2468 for potential clinical development. ACS Med Chem Lett. 2014, 5: 124-127. 10.1021/ml400359z.CrossRefPubMed Zhang Z, Chu XJ, Liu JJ, Ding Q, Zhang J, Bartkovitz D, Jiang N, Karnachi P, So SS, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassiley L, Graves B: Discovery of potent and orally active p53-MDM2 inhibitors RO5353 and RO2468 for potential clinical development. ACS Med Chem Lett. 2014, 5: 124-127. 10.1021/ml400359z.CrossRefPubMed
9.
go back to reference Nijman SMB, Luna-Vargas MPA, Velds A, Brummelkamp TR, Dirac AMG, Sixma TK, Bernards R: A genomic and functional inventory of deubiquitinating enzymes. Cell. 2005, 123: 773-786. 10.1016/j.cell.2005.11.007.CrossRefPubMed Nijman SMB, Luna-Vargas MPA, Velds A, Brummelkamp TR, Dirac AMG, Sixma TK, Bernards R: A genomic and functional inventory of deubiquitinating enzymes. Cell. 2005, 123: 773-786. 10.1016/j.cell.2005.11.007.CrossRefPubMed
10.
go back to reference Baek KH: Conjugation and deconjugation of ubiquitin regulating the destiny of proteins. Exp Mol Med. 2003, 35: 1-7. 10.1038/emm.2003.1.CrossRefPubMed Baek KH: Conjugation and deconjugation of ubiquitin regulating the destiny of proteins. Exp Mol Med. 2003, 35: 1-7. 10.1038/emm.2003.1.CrossRefPubMed
11.
go back to reference Priolo C, Tang D, Brahamandan M, Benassi B, Sicinska E, Ogino S, Farsetti A, Porrello A, Finn S, Zimmermann J, Febbo P, Loda M: The isopeptidase USP2a protects human prostate cancer from apoptosis. Cancer Res. 2006, 66: 8625-8632. 10.1158/0008-5472.CAN-06-1374.CrossRefPubMed Priolo C, Tang D, Brahamandan M, Benassi B, Sicinska E, Ogino S, Farsetti A, Porrello A, Finn S, Zimmermann J, Febbo P, Loda M: The isopeptidase USP2a protects human prostate cancer from apoptosis. Cancer Res. 2006, 66: 8625-8632. 10.1158/0008-5472.CAN-06-1374.CrossRefPubMed
12.
go back to reference Oliveira AM, Chou MM, Perez-Atayde AR, Rosenberg AE: Aneurysmal bone cyst: a neoplasm driven by upregulation of the USP6 oncogene. J Clin Oncol. 2006, 24: e1-10.1200/JCO.2005.04.4818. author reply e2CrossRefPubMed Oliveira AM, Chou MM, Perez-Atayde AR, Rosenberg AE: Aneurysmal bone cyst: a neoplasm driven by upregulation of the USP6 oncogene. J Clin Oncol. 2006, 24: e1-10.1200/JCO.2005.04.4818. author reply e2CrossRefPubMed
13.
go back to reference Cummins JM, Rago C, Kohli M, Kinzler KW, Lengauer C, Vogelstein B: Tumour suppression: disruption of HAUSP gene stabilizes p53. Nature. 2004, 428: 1-10.1038/nature02501. p following 486CrossRefPubMed Cummins JM, Rago C, Kohli M, Kinzler KW, Lengauer C, Vogelstein B: Tumour suppression: disruption of HAUSP gene stabilizes p53. Nature. 2004, 428: 1-10.1038/nature02501. p following 486CrossRefPubMed
14.
go back to reference Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ: Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature. 2007, 446: 876-881. 10.1038/nature05694.CrossRefPubMed Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ: Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature. 2007, 446: 876-881. 10.1038/nature05694.CrossRefPubMed
15.
go back to reference Nguyen DX, Bos PD, Massague J: Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009, 9: 274-284. 10.1038/nrc2622.CrossRefPubMed Nguyen DX, Bos PD, Massague J: Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009, 9: 274-284. 10.1038/nrc2622.CrossRefPubMed
16.
go back to reference Massagué J, Gomis RR: The logic of TGFβ signaling. FEBS Letters. 2006, 580: 2811-2820. 10.1016/j.febslet.2006.04.033.CrossRefPubMed Massagué J, Gomis RR: The logic of TGFβ signaling. FEBS Letters. 2006, 580: 2811-2820. 10.1016/j.febslet.2006.04.033.CrossRefPubMed
17.
go back to reference Al-Salihi MA, Herhaus L, Sapkota GP: Regulation of the transforming growth factor β pathway by reversible ubiquitylation. Open Biol. 2012, 2: 120082-10.1098/rsob.120082.CrossRefPubMedPubMedCentral Al-Salihi MA, Herhaus L, Sapkota GP: Regulation of the transforming growth factor β pathway by reversible ubiquitylation. Open Biol. 2012, 2: 120082-10.1098/rsob.120082.CrossRefPubMedPubMedCentral
18.
go back to reference Dupont S, Inui M, Newfeld SJ: Regulation of TGF-β signal transduction by mono- and deubiquitylation of Smads. FEBS Lett. 2012, 586: 1913-1920. 10.1016/j.febslet.2012.03.037.CrossRefPubMedPubMedCentral Dupont S, Inui M, Newfeld SJ: Regulation of TGF-β signal transduction by mono- and deubiquitylation of Smads. FEBS Lett. 2012, 586: 1913-1920. 10.1016/j.febslet.2012.03.037.CrossRefPubMedPubMedCentral
20.
go back to reference Al-Salihi MA, Herhaus L, Macartney T, Sapkota GP: USP11 augments TGFbeta signalling by deubiquitylating ALK5. Open Biol. 2012, 2: 120063-10.1098/rsob.120063.CrossRefPubMedPubMedCentral Al-Salihi MA, Herhaus L, Macartney T, Sapkota GP: USP11 augments TGFbeta signalling by deubiquitylating ALK5. Open Biol. 2012, 2: 120063-10.1098/rsob.120063.CrossRefPubMedPubMedCentral
21.
go back to reference Eichhorn PJ, Rodon L, Gonzalez-Junca A, Dirac A, Gili M, Martinez-Saez E, Aura C, Barba I, Peg V, Prat A, Cuartas I, Jimenez J, Garcia-Dorado D, Sahuquillo J, Bernards R, Baselga J, Seoane J: USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the activation of TGF-beta signaling in glioblastoma. Nat Med. 2012, 18: 429-435. 10.1038/nm.2619.CrossRefPubMed Eichhorn PJ, Rodon L, Gonzalez-Junca A, Dirac A, Gili M, Martinez-Saez E, Aura C, Barba I, Peg V, Prat A, Cuartas I, Jimenez J, Garcia-Dorado D, Sahuquillo J, Bernards R, Baselga J, Seoane J: USP15 stabilizes TGF-beta receptor I and promotes oncogenesis through the activation of TGF-beta signaling in glioblastoma. Nat Med. 2012, 18: 429-435. 10.1038/nm.2619.CrossRefPubMed
22.
go back to reference Zhang L, Zhou F, Drabsch Y, Gao R, Snaar-Jagalska BE, Mickanin C, Huang H, Sheppard KA, Porter JA, Lu CX, ten Dijke P: USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-beta type I receptor. Nat Cell Biol. 2012, 14: 717-726. 10.1038/ncb2522.CrossRefPubMed Zhang L, Zhou F, Drabsch Y, Gao R, Snaar-Jagalska BE, Mickanin C, Huang H, Sheppard KA, Porter JA, Lu CX, ten Dijke P: USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-beta type I receptor. Nat Cell Biol. 2012, 14: 717-726. 10.1038/ncb2522.CrossRefPubMed
23.
go back to reference Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S: FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 2009, 136: 123-135. 10.1016/j.cell.2008.10.051.CrossRefPubMed Dupont S, Mamidi A, Cordenonsi M, Montagner M, Zacchigna L, Adorno M, Martello G, Stinchfield MJ, Soligo S, Morsut L, Inui M, Moro S, Modena N, Argenton F, Newfeld SJ, Piccolo S: FAM/USP9x, a deubiquitinating enzyme essential for TGFbeta signaling, controls Smad4 monoubiquitination. Cell. 2009, 136: 123-135. 10.1016/j.cell.2008.10.051.CrossRefPubMed
24.
go back to reference Xie Y, Avello M, Schirle M, McWhinnie E, Feng Y, Bric-Furlong E, Wilson C, Nathans R, Zhang J, Kirschner MW, Huang SM, Cong F: Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation. J Biol Chem. 2013, 288: 2976-2985. 10.1074/jbc.M112.430066.CrossRefPubMed Xie Y, Avello M, Schirle M, McWhinnie E, Feng Y, Bric-Furlong E, Wilson C, Nathans R, Zhang J, Kirschner MW, Huang SM, Cong F: Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation. J Biol Chem. 2013, 288: 2976-2985. 10.1074/jbc.M112.430066.CrossRefPubMed
25.
go back to reference Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K: Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001, 276: 12477-12480. 10.1074/jbc.C100008200.CrossRefPubMed Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, Miyazono K: Smurf1 interacts with transforming growth factor-β type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001, 276: 12477-12480. 10.1074/jbc.C100008200.CrossRefPubMed
26.
go back to reference Wang H-R, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, Thomsen GH, Wrana JL: Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science. 2003, 302: 1775-1779. 10.1126/science.1090772.CrossRefPubMed Wang H-R, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, Thomsen GH, Wrana JL: Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science. 2003, 302: 1775-1779. 10.1126/science.1090772.CrossRefPubMed
27.
go back to reference Stegeman S, Jolly LA, Premarathne S, Gecz J, Richards LJ, Mackay-Sim A, Wood SA: Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFbeta-mediated axonogenesis. PloS One. 2013, 8: e68287-10.1371/journal.pone.0068287.CrossRefPubMedPubMedCentral Stegeman S, Jolly LA, Premarathne S, Gecz J, Richards LJ, Mackay-Sim A, Wood SA: Loss of Usp9x disrupts cortical architecture, hippocampal development and TGFbeta-mediated axonogenesis. PloS One. 2013, 8: e68287-10.1371/journal.pone.0068287.CrossRefPubMedPubMedCentral
28.
go back to reference Fan YH, Yu Y, Mao RF, Tan XJ, Xu GF, Zhang H, Lu XB, Fu SB, Yang J: USP4 targets TAK1 to downregulate TNFalpha-induced NF-kappaB activation. Cell Death Differ. 2011, 18: 1547-1560. 10.1038/cdd.2011.11.CrossRefPubMedPubMedCentral Fan YH, Yu Y, Mao RF, Tan XJ, Xu GF, Zhang H, Lu XB, Fu SB, Yang J: USP4 targets TAK1 to downregulate TNFalpha-induced NF-kappaB activation. Cell Death Differ. 2011, 18: 1547-1560. 10.1038/cdd.2011.11.CrossRefPubMedPubMedCentral
29.
go back to reference Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X, Fan Y, Yu Y, Burlingame S, Zhang H, Fu S, Cao G, Qin J, Yang J: USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal. 2010, 22: 386-394. 10.1016/j.cellsig.2009.10.008.CrossRefPubMedPubMedCentral Sun W, Tan X, Shi Y, Xu G, Mao R, Gu X, Fan Y, Yu Y, Burlingame S, Zhang H, Fu S, Cao G, Qin J, Yang J: USP11 negatively regulates TNFalpha-induced NF-kappaB activation by targeting on IkappaBalpha. Cell Signal. 2010, 22: 386-394. 10.1016/j.cellsig.2009.10.008.CrossRefPubMedPubMedCentral
30.
go back to reference Schweitzer K, Bozko PM, Dubiel W, Naumann M: CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha. EMBO J. 2007, 26: 1532-1541. 10.1038/sj.emboj.7601600.CrossRefPubMedPubMedCentral Schweitzer K, Bozko PM, Dubiel W, Naumann M: CSN controls NF-kappaB by deubiquitinylation of IkappaBalpha. EMBO J. 2007, 26: 1532-1541. 10.1038/sj.emboj.7601600.CrossRefPubMedPubMedCentral
31.
go back to reference Hayes SD, Liu H, MacDonald E, Sanderson CM, Coulson JM, Clague MJ, Urbe S: Direct and indirect control of mitogen-activated protein kinase pathway-associated components, BRAP/IMP E3 ubiquitin ligase and CRAF/RAF1 kinase, by the deubiquitylating enzyme USP15. J Biol Chem. 2012, 287: 43007-43018. 10.1074/jbc.M112.386938.CrossRefPubMedPubMedCentral Hayes SD, Liu H, MacDonald E, Sanderson CM, Coulson JM, Clague MJ, Urbe S: Direct and indirect control of mitogen-activated protein kinase pathway-associated components, BRAP/IMP E3 ubiquitin ligase and CRAF/RAF1 kinase, by the deubiquitylating enzyme USP15. J Biol Chem. 2012, 287: 43007-43018. 10.1074/jbc.M112.386938.CrossRefPubMedPubMedCentral
32.
go back to reference Inui M, Manfrin A, Mamidi A, Martello G, Morsut L, Soligo S, Enzo E, Moro S, Polo S, Dupont S, Cordenonsi M, Piccolo S: USP15 is a deubiquitylating enzyme for receptor-activated SMADs. Nat Cell Biol. 2011, 13: 1368-1375. 10.1038/ncb2346.CrossRefPubMed Inui M, Manfrin A, Mamidi A, Martello G, Morsut L, Soligo S, Enzo E, Moro S, Polo S, Dupont S, Cordenonsi M, Piccolo S: USP15 is a deubiquitylating enzyme for receptor-activated SMADs. Nat Cell Biol. 2011, 13: 1368-1375. 10.1038/ncb2346.CrossRefPubMed
33.
go back to reference Zhang L, Zhou F, Garcia de Vinuesa A, de Kruijf EM, Mesker WE, Hui L, Drabsch Y, Li Y, Bauer A, Rousseau A, Sheppard KA, Mickanin C, Kuppen PJ, Lu CX, Ten Dijke P: TRAF4 promotes TGF-beta receptor signaling and drives breast cancer metastasis. Mol Cell. 2013, 51: 559-572. 10.1016/j.molcel.2013.07.014.CrossRefPubMed Zhang L, Zhou F, Garcia de Vinuesa A, de Kruijf EM, Mesker WE, Hui L, Drabsch Y, Li Y, Bauer A, Rousseau A, Sheppard KA, Mickanin C, Kuppen PJ, Lu CX, Ten Dijke P: TRAF4 promotes TGF-beta receptor signaling and drives breast cancer metastasis. Mol Cell. 2013, 51: 559-572. 10.1016/j.molcel.2013.07.014.CrossRefPubMed
34.
go back to reference Zhang Y, Martens JWM, Yu JX, Jiang J, Sieuwerts AM, Smid M, Klijn JGM, Wang Y, Foekens JA: Copy number alterations that predict metastatic capability of human breast cancer. Cancer Res. 2009, 69: 3795-3801. 10.1158/0008-5472.CAN-08-4596.CrossRefPubMed Zhang Y, Martens JWM, Yu JX, Jiang J, Sieuwerts AM, Smid M, Klijn JGM, Wang Y, Foekens JA: Copy number alterations that predict metastatic capability of human breast cancer. Cancer Res. 2009, 69: 3795-3801. 10.1158/0008-5472.CAN-08-4596.CrossRefPubMed
35.
go back to reference Akhavantabasi S, Akman HB, Sapmaz A, Keller J, Petty EM, Erson AE: USP32 is an active, membrane-bound ubiquitin protease overexpressed in breast cancers. Mamm Genome. 2010, 21: 388-397. 10.1007/s00335-010-9268-4.CrossRefPubMed Akhavantabasi S, Akman HB, Sapmaz A, Keller J, Petty EM, Erson AE: USP32 is an active, membrane-bound ubiquitin protease overexpressed in breast cancers. Mamm Genome. 2010, 21: 388-397. 10.1007/s00335-010-9268-4.CrossRefPubMed
36.
go back to reference Schulte I, Batty EM, Pole JC, Blood KA, Mo S, Cooke SL, Ng C, Howe KL, Chin SF, Brenton JD, Caldas C, Howarth KD, Edwards PA: Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes. BMC Genomics. 2012, 13: 719-10.1186/1471-2164-13-719.CrossRefPubMedPubMedCentral Schulte I, Batty EM, Pole JC, Blood KA, Mo S, Cooke SL, Ng C, Howe KL, Chin SF, Brenton JD, Caldas C, Howarth KD, Edwards PA: Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes. BMC Genomics. 2012, 13: 719-10.1186/1471-2164-13-719.CrossRefPubMedPubMedCentral
37.
go back to reference Schoenfeld AR, Apgar S, Dolios G, Wang R, Aaronson SA: 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: 7444-7455. 10.1128/MCB.24.17.7444-7455.2004.CrossRefPubMedPubMedCentral Schoenfeld AR, Apgar S, Dolios G, Wang R, Aaronson SA: 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: 7444-7455. 10.1128/MCB.24.17.7444-7455.2004.CrossRefPubMedPubMedCentral
38.
go back to reference Roy R, Chun J, Powell SN: BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2012, 12: 68-78. 10.1038/nrc3181.CrossRef Roy R, Chun J, Powell SN: BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat Rev Cancer. 2012, 12: 68-78. 10.1038/nrc3181.CrossRef
39.
go back to reference Njiaju UO, Olopade OI: Genetic determinants of breast cancer risk: a review of current literature and issues pertaining to clinical application. Breast J. 2012, 18: 436-442. 10.1111/j.1524-4741.2012.01274.x.CrossRefPubMed Njiaju UO, Olopade OI: Genetic determinants of breast cancer risk: a review of current literature and issues pertaining to clinical application. Breast J. 2012, 18: 436-442. 10.1111/j.1524-4741.2012.01274.x.CrossRefPubMed
40.
go back to reference Wiltshire TD, Lovejoy CA, Wang T, Xia F, O'Connor MJ, Cortez D: Sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition identifies ubiquitin-specific peptidase 11 (USP11) as a regulator of DNA double-strand break repair. J Biol Chem. 2010, 285: 14565-14571. 10.1074/jbc.M110.104745.CrossRefPubMedPubMedCentral Wiltshire TD, Lovejoy CA, Wang T, Xia F, O'Connor MJ, Cortez D: Sensitivity to poly(ADP-ribose) polymerase (PARP) inhibition identifies ubiquitin-specific peptidase 11 (USP11) as a regulator of DNA double-strand break repair. J Biol Chem. 2010, 285: 14565-14571. 10.1074/jbc.M110.104745.CrossRefPubMedPubMedCentral
41.
go back to reference Bayraktar S, Gutierrez Barrera AM, Liu D, Pusztai L, Litton J, Valero V, Hunt K, Hortobagyi GN, Wu Y, Symmans F, Arun B: USP-11 as a predictive and prognostic factor following neoadjuvant therapy in women with breast cancer. Cancer J. 2013, 19: 10-17. 10.1097/PPO.0b013e3182801b3a.CrossRefPubMedPubMedCentral Bayraktar S, Gutierrez Barrera AM, Liu D, Pusztai L, Litton J, Valero V, Hunt K, Hortobagyi GN, Wu Y, Symmans F, Arun B: USP-11 as a predictive and prognostic factor following neoadjuvant therapy in women with breast cancer. Cancer J. 2013, 19: 10-17. 10.1097/PPO.0b013e3182801b3a.CrossRefPubMedPubMedCentral
42.
go back to reference Deng S, Zhou H, Xiong R, Lu Y, Yan D, Xing T, Dong L, Tang E, Yang H: Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics. Breast Cancer Res Treatment. 2007, 104: 21-30. 10.1007/s10549-006-9393-7.CrossRef Deng S, Zhou H, Xiong R, Lu Y, Yan D, Xing T, Dong L, Tang E, Yang H: Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics. Breast Cancer Res Treatment. 2007, 104: 21-30. 10.1007/s10549-006-9393-7.CrossRef
43.
go back to reference Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, Maecker H, O'Rourke K, Bazan F, Eastham-Anderson J, Yue P, Dornan D, Huang DC, Dixit VM: Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010, 463: 103-107. 10.1038/nature08646.CrossRefPubMed Schwickart M, Huang X, Lill JR, Liu J, Ferrando R, French DM, Maecker H, O'Rourke K, Bazan F, Eastham-Anderson J, Yue P, Dornan D, Huang DC, Dixit VM: Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010, 463: 103-107. 10.1038/nature08646.CrossRefPubMed
44.
go back to reference Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, Wang H-G, Zhang X, Bullrich F, Croce CM, Rai K, Hines J, Reed JC: Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood. 1998, 91: 3379-3389.PubMed Kitada S, Andersen J, Akar S, Zapata JM, Takayama S, Krajewski S, Wang H-G, Zhang X, Bullrich F, Croce CM, Rai K, Hines J, Reed JC: Expression of apoptosis-regulating proteins in chronic lymphocytic leukemia: correlations with in vitro and in vivo chemoresponses. Blood. 1998, 91: 3379-3389.PubMed
45.
go back to reference Wuilleme-Toumi S, Robillard N, Gomez P, Moreau P, Le Gouill S, Avet-Loiseau H, Harousseau JL, Amiot M, Bataille R: Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival. Leukemia. 2005, 19: 1248-1252. 10.1038/sj.leu.2403784.CrossRefPubMed Wuilleme-Toumi S, Robillard N, Gomez P, Moreau P, Le Gouill S, Avet-Loiseau H, Harousseau JL, Amiot M, Bataille R: Mcl-1 is overexpressed in multiple myeloma and associated with relapse and shorter survival. Leukemia. 2005, 19: 1248-1252. 10.1038/sj.leu.2403784.CrossRefPubMed
46.
go back to reference Ding Q, He X, Xia W, Hsu J-M, Chen C-T, Li L-Y, Lee D-F, Yang J-Y, Xie X, Liu J-C, Hung MC: Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3β activity and associates with poor prognosis in human breast cancer. Cancer Res. 2007, 67: 4564-4571. 10.1158/0008-5472.CAN-06-1788.CrossRefPubMed Ding Q, He X, Xia W, Hsu J-M, Chen C-T, Li L-Y, Lee D-F, Yang J-Y, Xie X, Liu J-C, Hung MC: Myeloid cell leukemia-1 inversely correlates with glycogen synthase kinase-3β activity and associates with poor prognosis in human breast cancer. Cancer Res. 2007, 67: 4564-4571. 10.1158/0008-5472.CAN-06-1788.CrossRefPubMed
47.
48.
go back to reference Peddaboina C, Jupiter D, Fletcher S, Yap JL, Rai A, Tobin RP, Jiang W, Rascoe P, Rogers MK, Smythe WR, Cao X: The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition. BMC Cancer. 2012, 12: 541-10.1186/1471-2407-12-541.CrossRefPubMedPubMedCentral Peddaboina C, Jupiter D, Fletcher S, Yap JL, Rai A, Tobin RP, Jiang W, Rascoe P, Rogers MK, Smythe WR, Cao X: The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition. BMC Cancer. 2012, 12: 541-10.1186/1471-2407-12-541.CrossRefPubMedPubMedCentral
49.
go back to reference Harris DR, Mims A, Bunz F: Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil. Cancer Biol Ther. 2012, 13: 1319-1324. 10.4161/cbt.21792.CrossRefPubMedPubMedCentral Harris DR, Mims A, Bunz F: Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil. Cancer Biol Ther. 2012, 13: 1319-1324. 10.4161/cbt.21792.CrossRefPubMedPubMedCentral
50.
go back to reference Cox JL, Wilder PJ, Gilmore JM, Wuebben EL, Washburn MP, Rizzino A: The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells. PLoS One. 2013, 8: e62857-10.1371/journal.pone.0062857.CrossRefPubMedPubMedCentral Cox JL, Wilder PJ, Gilmore JM, Wuebben EL, Washburn MP, Rizzino A: The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells. PLoS One. 2013, 8: e62857-10.1371/journal.pone.0062857.CrossRefPubMedPubMedCentral
51.
go back to reference Yuan J, Luo K, Zhang L, Cheville JC, Lou Z: USP10 regulates p53 localization and stability by deubiquitinating p53. Cell. 2010, 140: 384-396. 10.1016/j.cell.2009.12.032.CrossRefPubMedPubMedCentral Yuan J, Luo K, Zhang L, Cheville JC, Lou Z: USP10 regulates p53 localization and stability by deubiquitinating p53. Cell. 2010, 140: 384-396. 10.1016/j.cell.2009.12.032.CrossRefPubMedPubMedCentral
52.
go back to reference Niu J, Shi Y, Xue J, Miao R, Huang S, Wang T, Wu J, Fu M, Wu ZH: USP10 inhibits genotoxic NF-kappaB activation by MCPIP1-facilitated deubiquitination of NEMO. EMBO J. 2013, 32: 3206-3219. 10.1038/emboj.2013.247.CrossRefPubMedPubMedCentral Niu J, Shi Y, Xue J, Miao R, Huang S, Wang T, Wu J, Fu M, Wu ZH: USP10 inhibits genotoxic NF-kappaB activation by MCPIP1-facilitated deubiquitination of NEMO. EMBO J. 2013, 32: 3206-3219. 10.1038/emboj.2013.247.CrossRefPubMedPubMedCentral
53.
go back to reference Zhong B, Liu X, Wang X, Li H, Darnay BG, Lin X, Sun SC, Dong C: Ubiquitin-specific protease 25 regulates TLR4-dependent innate immune responses through deubiquitination of the adaptor protein TRAF3. Sci Signal. 2013, 6: ra35-10.1016/j.sigpro.2012.06.015.CrossRefPubMed Zhong B, Liu X, Wang X, Li H, Darnay BG, Lin X, Sun SC, Dong C: Ubiquitin-specific protease 25 regulates TLR4-dependent innate immune responses through deubiquitination of the adaptor protein TRAF3. Sci Signal. 2013, 6: ra35-10.1016/j.sigpro.2012.06.015.CrossRefPubMed
54.
go back to reference Colland F, Formstecher E, Jacq X, Reverdy C, Planquette C, Conrath S, Trouplin V, Bianchi J, Aushev VN, Camonis J, Calabrese A, Borg-Capra C, Sippl W, Collura V, Boissy G, Rain JC, Guedat P, Delansorne R, Daviet L: Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther. 2009, 8: 2286-2295. 10.1158/1535-7163.MCT-09-0097.CrossRefPubMed Colland F, Formstecher E, Jacq X, Reverdy C, Planquette C, Conrath S, Trouplin V, Bianchi J, Aushev VN, Camonis J, Calabrese A, Borg-Capra C, Sippl W, Collura V, Boissy G, Rain JC, Guedat P, Delansorne R, Daviet L: Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol Cancer Ther. 2009, 8: 2286-2295. 10.1158/1535-7163.MCT-09-0097.CrossRefPubMed
55.
go back to reference Peterson LF, Mitrikeska E, Giannola D, Lui Y, Sun H, Bixby D, Malek SN, Donato NJ, Wang S, Talpaz M: p53 stabilization induces apoptosis in chronic myeloid leukemia blast crisis cells. Leukemia. 2011, 25: 761-769. 10.1038/leu.2011.7.CrossRefPubMed Peterson LF, Mitrikeska E, Giannola D, Lui Y, Sun H, Bixby D, Malek SN, Donato NJ, Wang S, Talpaz M: p53 stabilization induces apoptosis in chronic myeloid leukemia blast crisis cells. Leukemia. 2011, 25: 761-769. 10.1038/leu.2011.7.CrossRefPubMed
56.
go back to reference Nocito A, Kononen J, Kallioniemi OP, Sauter G: Tissue microarrays (TMAs) for high-throughput molecular pathology research. Int J Cancer. 2001, 94: 1-5. 10.1002/ijc.1385.CrossRefPubMed Nocito A, Kononen J, Kallioniemi OP, Sauter G: Tissue microarrays (TMAs) for high-throughput molecular pathology research. Int J Cancer. 2001, 94: 1-5. 10.1002/ijc.1385.CrossRefPubMed
57.
go back to reference Chen J, Dexheimer TS, Ai Y, Liang Q, Villamil MA, Inglese J, Maloney DJ, Jadhav A, Simeonov A, Zhuang Z: Selective and cell-active inhibitors of the USP1/ UAF1 deubiquitinase complex reverse cisplatin resistance in non-small cell lung cancer cells. Chem Biol. 2011, 18: 1390-1400. 10.1016/j.chembiol.2011.08.014.CrossRefPubMedPubMedCentral Chen J, Dexheimer TS, Ai Y, Liang Q, Villamil MA, Inglese J, Maloney DJ, Jadhav A, Simeonov A, Zhuang Z: Selective and cell-active inhibitors of the USP1/ UAF1 deubiquitinase complex reverse cisplatin resistance in non-small cell lung cancer cells. Chem Biol. 2011, 18: 1390-1400. 10.1016/j.chembiol.2011.08.014.CrossRefPubMedPubMedCentral
58.
go back to reference Liang Q, Dexheimer TS, Zhang P, Rosenthal AS, Villamil MA, You C, Zhang Q, Chen J, Ott CA, Sun H, Luci DK, Yuan B, Simeonov A, Jadhav A, Xiao H, Wang Y, Maloney DJ, Zhuang Z: A selective USP1–UAF1 inhibitor links deubiquitination to DNA damage responses. Nat Chem Biol. 2014, 10: 298-304. 10.1038/nchembio.1455.CrossRefPubMedPubMedCentral Liang Q, Dexheimer TS, Zhang P, Rosenthal AS, Villamil MA, You C, Zhang Q, Chen J, Ott CA, Sun H, Luci DK, Yuan B, Simeonov A, Jadhav A, Xiao H, Wang Y, Maloney DJ, Zhuang Z: A selective USP1–UAF1 inhibitor links deubiquitination to DNA damage responses. Nat Chem Biol. 2014, 10: 298-304. 10.1038/nchembio.1455.CrossRefPubMedPubMedCentral
59.
go back to reference Lo MC, Peterson LF, Yan M, Cong X, Hickman JH, Dekelver RC, Niewerth D, Zhang DE: JAK inhibitors suppress t(8;21) fusion protein-induced leukemia. Leukemia. 2013, 27: 2272-2279. 10.1038/leu.2013.197.CrossRefPubMedPubMedCentral Lo MC, Peterson LF, Yan M, Cong X, Hickman JH, Dekelver RC, Niewerth D, Zhang DE: JAK inhibitors suppress t(8;21) fusion protein-induced leukemia. Leukemia. 2013, 27: 2272-2279. 10.1038/leu.2013.197.CrossRefPubMedPubMedCentral
60.
go back to reference Edelmann MJ, Nicholson B, Kessler BM: Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases. Expert Rev Mol Med. 2011, 13: e35-10.1017/S1462399411002031.CrossRefPubMedPubMedCentral Edelmann MJ, Nicholson B, Kessler BM: Pharmacological targets in the ubiquitin system offer new ways of treating cancer, neurodegenerative disorders and infectious diseases. Expert Rev Mol Med. 2011, 13: e35-10.1017/S1462399411002031.CrossRefPubMedPubMedCentral
61.
go back to reference Colland F: The therapeutic potential of deubiquitinating enzyme inhibitors. Biochem Soc Trans. 2010, 38: 137-143. 10.1042/BST0380137.CrossRefPubMed Colland F: The therapeutic potential of deubiquitinating enzyme inhibitors. Biochem Soc Trans. 2010, 38: 137-143. 10.1042/BST0380137.CrossRefPubMed
Metadata
Title
Ubiquitin-specific proteases as therapeutic targets for the treatment of breast cancer
Authors
Anupama Pal
Nicholas J Donato
Publication date
01-10-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-014-0461-3

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