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The roles of ubiquitin modifying enzymes in neoplastic disease. (Biochim Biophys Acta, Sept 2017)

Kumari N1, Jaynes PW2, Saei A3, Iyengar PV2, Richard JLC2, Eichhorn PJA4.

Author information
1 Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
2 Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
3 Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore; Genome Institute of Singapore, A*STAR, Singapore.
4 Cancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore. Electronic address: pieter_eichhorn@nus.edu.sg.

Abstract
The initial experiments performed by Rose, Hershko, and Ciechanover describing the identification of a specific degradation signal in short-lived proteins paved the way to the discovery of the ubiquitin mediated regulation of numerous physiological functions required for cellular homeostasis. Since their discovery of ubiquitin and ubiquitin function over 30years ago it has become wholly apparent that ubiquitin and their respective ubiquitin modifying enzymes are key players in tumorigenesis. The human genome encodes approximately 600 putative E3 ligases and 80 deubiquitinating enzymes and in the majority of cases these enzymes exhibit specificity in sustaining either pro-tumorigenic or tumour repressive responses. In this review, we highlight the known oncogenic and tumour suppressive effects of ubiquitin modifying enzymes in cancer relevant pathways with specific focus on PI3K, MAPK, TGFβ, WNT, and YAP pathways. Moreover, we discuss the capacity of targeting DUBs as a novel anticancer therapeutic strategy.

KEYWORDS: Cancer; Deubiquitinating enzymes; Dub inhibitors; E3 ligases; Ubiquitin

PMID: 28923280