Caspase-9

Literature References: Central initiator caspase. Synthesized as an inactive 46 kDa precursor protein, procaspase-9, which consists of three domains: an N-terminal pro-domain, a 20 kDa large subunit, and a 10 kDa small subunit. Activated in the cytoplasm by cleavage of the prodomain, in response to mitochondrial damage. Activation occurs by binding to an Apaf-1/cytochrome c complex known as the apoptosome, in the presence of dATP. Isoln and characterization: H. Duan et al., J. Biol. Chem. 271, 16720 (1996); S. M. Srinivasula et al., ibid. 27099. Purification, binding to Apaf-1, and activation of caspase-3, q.v.: P. Li et al., Cell 91, 479 (1997). Role in initiation of the caspase cascade: E. A. Slee et al., J. Cell Biol. 144, 281 (1999). Crystal structure of the prodomain in complex with the prodomain of Apaf-1: H. Qin et al., Nature 399, 549 (1999). Human gene structure and chromosomal location: S. Hadano et al., Mammal. Genome 10, 757 (1999). Activation mechanism: J. Rodriguez, Y. Lazebnik, Genes Dev. 13, 3179 (1999); E. N. Shiozaki et al., Proc. Natl. Acad. Sci. USA 99, 4197 (2002). Review of structure and function: K. Kuida, Int. J. Biochem. Cell Biol. 32, 121-124 (2000); of activation mechanism: Y. Shi, Structure 10, 285-288 (2002).