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Deubiquitinating Enzymes As Oncotargets

Overview
Journal Oncotarget
Specialty Oncology
Date 2015 May 13
PMID 25962961
Citations 57
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Abstract

Carcinogenesis is a complex process tightly regulated at multiple levels by post-translational modifications. Epigenetics plays a major role in cancer development, all stable changes to the gene expression process that are not a result of a direct change in the DNA code are described as epigenetics. Epigenetic processes are regulated by post-translational modifications including ubiquitination which can directly affect either histones or transcription factors or may target their co-factors and interacting partners exerting an indirect effect. Deubiquitination of these target proteins is equally important and alterations in this pathway can also lead to cancer development, progression and metastasis. Only the correct, unaltered balance between ubiquitination and deubiquitination ensures healthy cellular homeostasis. In this review we focus on the role of deubiquitinating (DUB) enzymes in various aspects of epigenetics including the regulation of transcription factors, histone modifications, DNA damage repair pathways and cell cycle regulation. We discuss the impact of those processes on tumourigenesis and potential therapeutic applications of DUBs for cancer treatment.

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References
1.
Dexheimer T, Rosenthal A, Luci D, Liang Q, Villamil M, Chen J . Synthesis and structure-activity relationship studies of N-benzyl-2-phenylpyrimidin-4-amine derivatives as potent USP1/UAF1 deubiquitinase inhibitors with anticancer activity against nonsmall cell lung cancer. J Med Chem. 2014; 57(19):8099-110. PMC: 4191588. DOI: 10.1021/jm5010495. View

2.
Kim J, Parmar K, Huang M, Weinstock D, Ruit C, Kutok J . Inactivation of murine Usp1 results in genomic instability and a Fanconi anemia phenotype. Dev Cell. 2009; 16(2):314-20. PMC: 3134285. DOI: 10.1016/j.devcel.2009.01.001. View

3.
Villamil M, Liang Q, Zhuang Z . The WD40-repeat protein-containing deubiquitinase complex: catalysis, regulation, and potential for therapeutic intervention. Cell Biochem Biophys. 2013; 67(1):111-26. PMC: 3896570. DOI: 10.1007/s12013-013-9637-1. View

4.
Zhu P, Zhou W, Wang J, Puc J, Ohgi K, Erdjument-Bromage H . A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation. Mol Cell. 2007; 27(4):609-21. PMC: 2709280. DOI: 10.1016/j.molcel.2007.07.024. View

5.
Zhao B, Schlesiger C, Masucci M, Lindsten K . The ubiquitin specific protease 4 (USP4) is a new player in the Wnt signalling pathway. J Cell Mol Med. 2010; 13(8B):1886-95. PMC: 9181360. DOI: 10.1111/j.1582-4934.2009.00682.x. View