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

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.