Scientific background: |
CASP9 (CASPASE9), also called APAF3, is an initiator caspase, encoded by the CASP9 gene. The CASP9 gene is mapped to chromosome 1p36.3-p36.1 by FISH. CASP9 is identified as a member of the caspase family that participates in caspase-3 activation in vitro. And it also regarded as the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. Its genomic coordinates(GRCh37) is 1:15,818,768 - 15,851,284. The crystal structure of CASP9 is complex with the BIR3 in an inhibitory domain of XIAP at 2.4-angstrom resolution and the CASP9 gene contains 9 exons and spans approximately 35 kb of genomic DNA.Caspase-9 and APAF1 bind to each other via their respective NH2-terminal CED-3 homologous domains in the presence of cytochrome c and dATP, an event that leads to caspase-9 activation. CASP9 activity increases dramatically upon association with the apoptosome complex. And the majority of Casp9 knockout mice died perinatally with a markedly enlarged and malformed cerebrum caused by reduced apoptosis during brain development. |
References: |
1.Chew, S. K., Chen, P., Link, N., Galindo, K. A., Pogue, K., Abrams, J. M. Genome-wide silencing in Drosophila captures conserved apoptotic effectors. Nature 460: 123-127, 2009.
2.Hadano, S., Nasir, J., Nichol, K., Rasper, D. M., Vaillancourt, J. P., Sherer, S. W., Beatty, B. G., Ikeda, J.-E., Nicholson, D. W., Hayden, M. R. Genomic organization of the human caspase-9 gene on chromosome 1p36.1-p36.3. Mammalian Genome 10: 757-760, 1999.
3.Kuida, K., Haydar, T. F., Kuan, C.-Y., Gu, Y., Taya, C., Karasuyama, H., Su, M. S.-S., Rakic, P., Flavell, R. A. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94: 325-327, 1998.
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