A cyclin without cyclin-dependent kinases: cyclin F controls genome stability through ubiquitin-mediated proteolysis

Trends Cell Biol. 2013 Mar;23(3):135-40. doi: 10.1016/j.tcb.2012.10.011. Epub 2012 Nov 19.

Abstract

Cell cycle transitions are driven by the periodic oscillations of cyclins, which bind and activate cyclin-dependent kinases (CDKs) to phosphorylate target substrates. Cyclin F uses a substrate recruitment strategy similar to that of the other cyclins, but its associated catalytic activity is substantially different. Indeed, cyclin F is the founding member of the F-box family of proteins, which are the substrate recognition subunits of Skp1-Cul1-F-box protein (SCF) ubiquitin ligase complexes. Here, we discuss cyclin F function and recently identified substrates of SCF(cyclin)(F) involved in deoxyribonucleotide triphosphate (dNTP) production, centrosome duplication, and spindle formation. We highlight the relevance of cyclin F in controlling genome stability through ubiquitin-mediated proteolysis and the implications for cancer development.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cyclins / genetics*
  • Cyclins / metabolism
  • Gene Expression Regulation*
  • Genome, Human*
  • Genomic Instability*
  • Humans
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Proteolysis
  • Ribonucleoside Diphosphate Reductase / genetics
  • Ribonucleoside Diphosphate Reductase / metabolism
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Signal Transduction
  • Ubiquitin / genetics*
  • Ubiquitin / metabolism

Substances

  • CCNF protein, human
  • Cyclins
  • Protein Subunits
  • Ubiquitin
  • ribonucleotide reductase M2
  • Ribonucleoside Diphosphate Reductase
  • SKP Cullin F-Box Protein Ligases