Nuclear colocalization and interaction between bcl-xL and cdk1(cdc2) during G2/M cell-cycle checkpoint

Oncogene. 2007 Aug 30;26(40):5851-65. doi: 10.1038/sj.onc.1210396. Epub 2007 Mar 19.


In response to cancer chemotherapeutic drugs, cells rapidly trigger the apoptotic program or undergo growth arrest and senescence at specific phases of the cell cycle. Mitochondrial bcl-xL plays a central role in preventing alteration of mitochondrial dysfunction, cytochrome c release, caspase activation, DNA fragmentation and apoptosis. However, its pleitropic function depends on its subcellular localization. Here, we show that in addition to its mitochondrial effect that delays apoptosis, bcl-xL colocalizes and binds to cdk1(cdc2) during G(2)/M cell-cycle checkpoint and its overexpression stabilizes a G(2)/M-arrest senescence program in surviving cells after DNA damage. Bcl-xL potently inhibits cdk1(cdc2) kinase activity, which is reversible by a synthetic peptide between the 41st amino acid and 60th amino acid surrounding of the Thr47 and Ser62 phosphorylation sites, and Asn52 deamidation site, within the flexible loop domain of bcl-xL. A mutant deleted of this region does not alter the antiapoptotic function of bcl-xL, but impedes its effect on cdk1(cdc2) activity and on the G(2)/M-arrest senescence program after DNA damage. The nuclear interaction of bcl-xL and cdk1(cdc2) suggests that bcl-xL is coupled to the stabilization of a cell-cycle checkpoint induced by DNA damage, and this effect is genetically distinct from its function on apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CDC2 Protein Kinase / metabolism*
  • Cell Cycle
  • Cell Division
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cellular Senescence
  • DNA Fragmentation
  • G2 Phase
  • Humans
  • Kinetics
  • Phosphorylation
  • U937 Cells
  • bcl-X Protein / metabolism
  • bcl-X Protein / physiology*


  • bcl-X Protein
  • CDC2 Protein Kinase