Role of the COP1 protein in cancer development and therapy

Semin Cancer Biol. 2020 Dec;67(Pt 2):43-52. doi: 10.1016/j.semcancer.2020.02.001. Epub 2020 Feb 3.

Abstract

COP1, an E3 ubiquitin ligase, has been demonstrated to play a vital role in the regulation of cell proliferation, apoptosis and DNA repair. Accumulated evidence has revealed that COP1 is involved in carcinogenesis via targeting its substrates, including p53, c-Jun, ETS, β-catenin, STAT3, MTA1, p27, 14-3-3σ, and C/EBPα, for ubiquitination and degradation. COP1 can play tumor suppressive and oncogenic roles in human malignancies, urging us to summarize the functions of COP1 in tumorigenesis. In this review, we describe the structure of COP1 and its known substrates. Moreover, we dissect the function of COP1 by physiological (mouse models), pathological (human tumor specimens) and biochemical (ubiquitin substrates) Evidence. Furthermore, we discuss COP1 as a potential therapeutic target for cancer therapy.

Keywords: COP1; Carcinogenesis; E3 ligase; Oncoprotein; Therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Molecular Targeted Therapy
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • COP1 protein, human
  • Ubiquitin-Protein Ligases