APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway

Biosci Rep. 2016 Sep 16;36(5):e00377. doi: 10.1042/BSR20160152. Print 2016 Oct.

Abstract

The ubiquitin (Ub) ligase anaphase promoting complex/cyclosome (APC/C) and the tumour suppressor retinoblastoma protein (pRB) play key roles in cell cycle regulation. APC/C is a critical regulator of mitosis and G1-phase of the cell cycle whereas pRB keeps a check on proliferation by inhibiting transition to the S-phase. APC/C and pRB interact with each other via the co-activator of APC/C, FZR1, providing an alternative pathway of regulation of G1 to S transition by pRB using a post-translational mechanism. Both pRB and FZR1 have complex roles and are implicated not only in regulation of cell proliferation but also in differentiation, quiescence, apoptosis, maintenance of chromosomal integrity and metabolism. Both are also targeted by transforming viruses. We discuss recent advances in our understanding of the involvement of APC/C and pRB in cell cycle based decisions and how these insights will be useful for development of anti-cancer and anti-viral drugs.

Keywords: FZR1; LxCxE; anaphase promoting complex/cyclosome; cell cycle; human papilloma virus; retinoblastoma.

Publication types

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

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / genetics*
  • Anaphase-Promoting Complex-Cyclosome / metabolism
  • Apoptosis / genetics
  • Cdh1 Proteins / genetics*
  • Cdh1 Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Proliferation / genetics
  • G1 Phase / genetics
  • Humans
  • Mitosis / genetics
  • Proteasome Endopeptidase Complex / genetics*
  • Proteasome Endopeptidase Complex / metabolism
  • Retinoblastoma Protein / genetics*
  • Retinoblastoma Protein / metabolism
  • Ubiquitin / genetics
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Cdh1 Proteins
  • Retinoblastoma Protein
  • Ubiquitin
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex