Cyclin E Ablation in the Mouse

Cell. 2003 Aug 22;114(4):431-43. doi: 10.1016/s0092-8674(03)00645-7.

Abstract

E type cyclins (E1 and E2) are believed to drive cell entry into the S phase. It is widely assumed that the two E type cyclins are critically required for proliferation of all cell types. Here, we demonstrate that E type cyclins are largely dispensable for mouse development. However, endoreplication of trophoblast giant cells and megakaryocytes is severely impaired in the absence of cyclin E. Cyclin E-deficient cells proliferate actively under conditions of continuous cell cycling but are unable to reenter the cell cycle from the quiescent G(0) state. Molecular analyses revealed that cells lacking cyclin E fail to normally incorporate MCM proteins into DNA replication origins during G(0)-->S progression. We also found that cyclin E-deficient cells are relatively resistant to oncogenic transformation. These findings define a molecular function for E type cyclins in cell cycle reentry and reveal a differential requirement for cyclin E in normal versus oncogenic proliferation.

Publication types

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

MeSH terms

  • Animals
  • Cardiovascular Abnormalities
  • Cell Cycle / physiology
  • Cell Transformation, Neoplastic
  • Cyclin E / genetics*
  • Cyclin E / metabolism*
  • DNA Replication
  • Embryo, Mammalian / physiology*
  • Female
  • Gene Targeting
  • Male
  • Megakaryocytes / physiology
  • Mice
  • Mice, Knockout
  • Placenta / cytology
  • Placenta / metabolism
  • Pregnancy
  • Spermatogenesis / physiology
  • Trophoblasts / cytology
  • Trophoblasts / metabolism

Substances

  • Cyclin E