Cyclin E induction by genotoxic stress leads to apoptosis of hematopoietic cells

Oncogene. 2000 Jun 1;19(24):2828-35. doi: 10.1038/sj.onc.1203623.


Cyclin E is essential for progression through the G1 phase of the cell cycle and initiation of DNA replication by interacting with, and activating its catalytic partner, the cyclin-dependent kinase 2 (Cdk2). We found a substantial increase in cyclin E mRNA, accompanied by increased production of cyclin E protein and cyclin E/Cdk2 kinase activity in multiple myeloma and lymphoma cells following irradiation. Cyclin E expression increased early in a time and dose-dependent manner, with a three-fold induction reached 8 h following gamma-irradiation. Run-on analyses indicated a predominantly transcriptional regulation of cyclin E. Stable overexpression of cyclin E, but not cyclin D1, sensitized IM-9 cells to gamma-irradiation-induced apoptosis; in contrast, a dominant-negative Cdk2, prevented apoptosis. Irradiation of cyclin E overexpressing cells led to an enhanced caspase activation and exposure of the phosphatidylserine on the plasma membrane, two key markers of apoptosis, events which were completely abolished in cells expressing a dominant-negative Cdk2. This study identifies cyclin E as a target for activation by ionizing radiation and which plays a functional role in apoptosis of hematopoietic cells. Oncogene (2000) 19, 2828 - 2835

Publication types

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

MeSH terms

  • Apoptosis / radiation effects*
  • CDC2-CDC28 Kinases*
  • Cells, Cultured
  • Cyclin E / biosynthesis*
  • Cyclin E / genetics
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases / metabolism
  • Humans
  • Lymphoma, T-Cell / pathology
  • Multiple Myeloma / pathology
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Messenger / analysis
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / physiology


  • Cyclin E
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • Protein Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinases