Regulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase.
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Yuan ZM, Huang Y, Ishiko T, Kharbanda S, Weichselbaum R, Kufe D
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.
- PubMed ID
- 9037071 [ View in PubMed]
- Abstract
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.