c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.

Activation of the initiator caspase-9 is essential for induction of apoptosis by developmental signals, oncogenic transformation, and genotoxic stress. The c-Abl tyrosine kinase is also involved in the apoptotic response to DNA damage. The present results demonstrate that c-Abl binds directly to caspase-9. We show that c-Abl phosphorylates caspase-9 on ...
Tyr-153 in vitro and in cells treated with DNA damaging agents. Moreover, inhibition of c-Abl with STI571 blocked DNA damage-induced autoprocessing of caspase-9 to the p35 subunit and activation of caspase-3. Caspase-9(Y153F) also attenuated DNA damage-induced processing of caspase-9 to p35, activation of caspase-3, and apoptosis. These findings indicate that caspase-9 autoprocessing is regulated by c-Abl in the apoptotic response to genotoxic stress.
Mesh Terms:
Apoptosis, Benzamides, Caspase 9, Caspases, DNA Damage, Humans, Phosphorylation, Piperazines, Proto-Oncogene Proteins c-abl, Pyrimidines, U937 Cells
J. Biol. Chem.
Date: Mar. 25, 2005
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