Oncotarget

Reviews:

Deubiquitinating enzymes as oncotargets

Urszula L. McClurg and Craig N. Robson _

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Oncotarget. 2015; 6:9657-9668. https://doi.org/10.18632/oncotarget.3922

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Abstract

Urszula L. McClurg1 and Craig N. Robson1

1 Solid Tumour Target Discovery Laboratory, Newcastle Cancer Centre, Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne, UK

Correspondence to:

Craig N. Robson, email:

Keywords: deubiquitination, DUBs, cancer, epigenetics, chromatin, androgen receptor, histones

Received: March 09, 2015 Accepted: April 08, 2015 Published: April 23, 2015

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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