Open AccessRegulation of DNA damage-induced apoptosis by the c-Abl tyrosine kinase
Author(s) -
Zhi-Min Yuan,
Yufan Huang,
Takatoshi Ishiko,
Surender Kharbanda,
Ralph R. Weichselbaum,
Donald Küfe
Publication year - 1997
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.94.4.1437
Subject(s) - apoptosis , dna damage , tyrosine kinase , microbiology and biotechnology , biology , abl , cancer research , transfection , chemistry , signal transduction , dna , cell culture , biochemistry , genetics
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.