Cyclin E

Int J Biochem Cell Biol. 2004 Aug;36(8):1424-39. doi: 10.1016/j.biocel.2003.12.005.


E-type cyclins (cyclin E1 and cyclin E2) are expressed during the late G1 phase of the cell cycle until the end of the S-phase. The activity of cyclin E is limiting for the passage of cells through the restriction point "R" which marks a "point of no return" for cells entering the division cycle from a resting state or passing from G1 into S-phase. Expression of cyclin E is regulated on the level of gene transcription mainly by members of the E2F trrnscription factor family and by its degradation via the proteasome pathway. Cyclin E binds and activates the kinase Cdk2 and by phosphorylating its substrates, the so-called "pocket proteins", the cyclic/Cdk2 complexes initiate a cascade of events that leads to the expression of S-phase specific genes. Aside from this specific function as a regulator of S-phase-entry, cyclin E plays a direct role in the initiation of DNA replication, the control of genomic stability, and the centrosome cycle. Surprisingly, recent studies have shown that the once thought essential cyclin E is dispensable for the development of higher eukaryotes and for the mitotic division of eukaryotic cells. Nevertheless, high level cyclin E expression has been associated with the initiation or progression of different human cancers, in particular breast cancer but also leukemia, lymphoma and others. Transgenic mouse models in which cyclin E is constitutively expressed develop malignant diseases, supporting the notion of cyclin E as a dominant onco-protein.

Publication types

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

MeSH terms

  • Animals
  • CDC2-CDC28 Kinases / metabolism
  • CDC2-CDC28 Kinases / physiology
  • Cyclin E* / chemistry
  • Cyclin E* / genetics
  • Cyclin E* / metabolism
  • Cyclin E* / physiology
  • Cyclin-Dependent Kinase 2
  • Humans
  • Interphase
  • Neoplasms / etiology
  • Ubiquitin / metabolism


  • Cyclin E
  • Ubiquitin
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2