Identification of a Novel Cyclin Required for the Intrinsic Apoptosis Pathway in Lymphoid Cells

Cell Death Differ. 2009 Feb;16(2):230-43. doi: 10.1038/cdd.2008.145. Epub 2008 Oct 17.

Abstract

We have identified an early step common to pathways activated by different forms of intrinsic apoptosis stimuli. It requires de novo synthesis of a novel cyclin, cyclin O, that forms active complexes primarily with Cdk2 upon apoptosis induction in lymphoid cells. Cyclin O expression precedes glucocorticoid and gamma-radiation-induced apoptosis in vivo in mouse thymus and spleen, and its overexpression induces caspase-dependent apoptosis in cultured cells. Knocking down the endogenous expression of cyclin O by shRNA leads to the inhibition of glucocorticoid and DNA damage-induced apoptosis due to a failure in the activation of apical caspases while leaving CD95 death receptor-mediated apoptosis intact. Our data demonstrate that apoptosis induction in lymphoid cells is one of the physiological roles of cyclin O and it does not act by perturbing a normal cellular process such as the cell cycle, the DNA damage checkpoints or transcriptional response to glucocorticoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3 / metabolism
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase 2 / metabolism
  • Cyclins / metabolism*
  • DNA Glycosylases / metabolism
  • Gene Knockdown Techniques
  • Glucocorticoids / metabolism
  • Humans
  • Lymphocytes / metabolism
  • Lymphocytes / radiation effects
  • Mice
  • Mice, Transgenic

Substances

  • Cyclins
  • Glucocorticoids
  • cyclin O, mouse
  • Cyclin-Dependent Kinase 2
  • CCNO protein, human
  • DNA Glycosylases
  • Caspase 3
  • Caspases