Functional analysis of deubiquitylating enzymes in tumorigenesis and development

Ji Cheng, Jianping Guo, Brian J. North, Bin Wang, Chun Ping Cui, Hongchang Li, Kaixiong Tao, Lingqiang Zhang, W. Wei

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Deubiquitylating enzymes (DUBs) are proteases that remove the ubiquitin moiety from ubiquitylated substrates to antagonize the modification mediated by E3 ubiquitin ligases. Currently, DUBs have been found to play critical roles in the regulation of various physiological or pathological processes, such as embryogenesis, immune homeostasis, tumorigenesis and neurodegenerative diseases. Accumulating evidences have suggested that different DUBs exert distinct function such as oncogenic, tumor-suppressive or context-dependent roles in tumorigenesis, mainly by affecting the protein stability, enzymatic activity or subcellular localization of its substrates. Importantly, multiple potent inhibitors targeting the enzymatic activity of oncogenic DUBs have been developed and show promising anti-cancer efficacy in preclinical models. Thus, exploring the unique role of DUB enzymes and their downstream effectors will provide novel insights into the molecular basis of cancer development. Here, we review and summarize recent progress on DUB functional annotation, as well as its biochemical regulation, to provide a better understanding for cancer therapies by targeting DUBs.

Original languageEnglish (US)
Article number188312
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1872
Issue number2
DOIs
StatePublished - Dec 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Genetics
  • Cancer Research

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