APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis

Semin Cancer Biol. 2020 Dec;67(Pt 2):80-91. doi: 10.1016/j.semcancer.2020.03.001. Epub 2020 Mar 9.

Abstract

The anaphase promoting complex/ cyclosome (APC/C), is an evolutionarily conserved protein complex essential for cellular division due to its role in regulating the mitotic transition from metaphase to anaphase. In this review, we highlight recent work that has shed light on our understanding of the role of APC/C coactivators, Cdh1 and Cdc20, in cancer initiation and development. We summarize the current state of knowledge regarding APC/C structure and function, as well as the distinct ways Cdh1 and Cdc20 are dysregulated in human cancer. We also discuss APC/C inhibitors, novel approaches for targeting the APC/C as a cancer therapy, and areas for future work.

Keywords: Anaphase promoting complex/ cyclosome; Cancer; Cdc20; Cdh1; Genome instability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / antagonists & inhibitors
  • Anaphase-Promoting Complex-Cyclosome / chemistry
  • Anaphase-Promoting Complex-Cyclosome / genetics
  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Carbamates / pharmacology
  • Cdc20 Proteins / genetics
  • Cdc20 Proteins / metabolism*
  • Cdh1 Proteins / genetics
  • Cdh1 Proteins / metabolism*
  • Diamines / pharmacology
  • Genomic Instability
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms / genetics
  • Neoplasms / pathology*

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Carbamates
  • Cdc20 Proteins
  • Cdh1 Proteins
  • Diamines
  • FZR1 protein, human
  • apcin
  • CDC20 protein, human
  • Anaphase-Promoting Complex-Cyclosome