title: Deubiquitinating enzymes as oncotargets.
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.
authors.affiliation: Solid Tumour Target Discovery Laboratory, Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Urszula L
authors.initials: UL
authors.lastname: McClurg
authors.affiliation: Solid Tumour Target Discovery Laboratory, Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Robson
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000737:chemistry*; D006801:Humans; D051379:Mice; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D002843:Chromatin; D004247:DNA; D006657:Histones; D009687:Nuclear Proteins; D014157:Transcription Factors; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases; C526165:WDR48 protein, human; C579228:USP1 protein, human; C464569:USP7 protein, human
keywords: DUBs; androgen receptor; cancer; chromatin; deubiquitination; epigenetics; histones