Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators

J Cell Physiol. 2001 Apr;187(1):1-10. doi: 10.1002/1097-4652(2001)9999:9999<1::AID-JCP1049>3.0.CO;2-O.


Cell-cycle progression in all eukaryotes is driven by cyclin-dependent kinases (CDKs) and their cyclin partners. In vertebrates, the proper and timely duplication of the genome during S-phase relies on the coordinated activities of positive regulators such as CDK-cyclins and E2F, and negative regulators such as CDK inhibitors of the Cip/Kip and INK4 families. Recent and ongoing work indicates that many important regulators of G1- and S-phases are targeted for ubiquitination and subsequent degradation by the 26S proteasome. The proteolysis of key proteins during G1- and S-phases appears to be central for proper custodial regulation of DNA replication and the maintenance of cellular homeostasis in general. This review highlights the current literature regarding ubiquitin-mediated proteolysis of G1- and S-phase regulators and the control of events during the initiation and completion of DNA replication in vertebrates.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism
  • DNA Replication
  • G1 Phase
  • S Phase
  • Ubiquitins / physiology*
  • Yeasts / metabolism


  • Cell Cycle Proteins
  • Cyclins
  • Ubiquitins
  • Cyclin-Dependent Kinases