c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.
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Raina D, Pandey P, Ahmad R, Bharti A, Ren J, Kharbanda S, Weichselbaum R, Kufe D
c-Abl tyrosine kinase regulates caspase-9 autocleavage in the apoptotic response to DNA damage.
J Biol Chem. 2005 Mar 25;280(12):11147-51. Epub 2005 Jan 18.
- PubMed ID
- 15657060 [ View in PubMed]
- Abstract
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.