Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase

Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1437-40. doi: 10.1073/pnas.94.4.1437.


Activation of the c-Abl protein tyrosine kinase by certain DNA-damaging agents contributes to downregulation of Cdk2 and G1 arrest by a p53-dependent mechanism. The present work investigates the potential role of c-Abl in apoptosis induced by DNA damage. Transient transfection studies with wild-type, but not kinase-inactive, c-Abl demonstrate induction of apoptosis. Cells that stably express inactive c-Abl exhibit resistance to ionizing radiation-induced loss of clonogenic survival and apoptosis. Cells null for c-abl are also impaired in the apoptotic response to ionizing radiation. We further show that cells deficient in p53 undergo apoptosis in response to expression of c-Abl and exhibit decreases in radiation-induced apoptosis when expressing inactive c-Abl. These findings suggest that c-Abl kinase regulates DNA damage-induced apoptosis.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis*
  • DNA Damage*
  • Enzyme Activation
  • Fibroblasts / cytology
  • Humans
  • Mice
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Radiation Tolerance*
  • Radiation, Ionizing
  • Recombinant Proteins
  • Tumor Cells, Cultured


  • Recombinant Proteins
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl