Caspase-9 and Apaf-1 bind to each other, which leads to Caspase-9 activation. Activated caspase-9 cleaves and activates Caspase-3 that is one of the key proteases, being responsible for the proteolytic cleavage of many key proteins in apoptosis. Recently, a novel isoform of rat Caspase-9 has been identified in which the C terminus of full-length Caspase-9 is replaced with an alternative peptide sequence. This protein called, Casp-9-CTD (where CTD is carboxyl-terminal divergent) is expressed in multiple tissues, with the relative highest statement observed in ovary and heart. The variant C terminus of Casp-9-CTD in rat is derived from an alternative exon of the rat Caspase-9 gene. Casp-9-CTD was found primarily in the cytoplasm and was not detected in the nucleus. Caspase-9-CTD proenzyme is not processed in the cells and lacks apoptotic activity. The Casp-9-CTD transfected cells are resistant to caspases induction by cytochrome c, suggesting that Casp-9-CTD acts as a dominant-negative variant. Caspase 9 is a cysteine C14 endopeptidase that mediates oncogene and drug-induced apoptosis. It is activated upon binding to Apaf-1/cytochrome c and inhibited upon phosphorylation by the serine/ threonine kinase Akt. Activated caspase-9 cleaves downstream caspases such as Caspase-3, -6 and -7 initiating the caspase cascade. Like other caspases, Caspase-9 plays a critical role in mediating apoptosis during normal brain development. Caspase-9 also cleaves amyloid beta-protein precursors, principal constituent of senile plaques, and is involved in neuronal death observed in Alzheimer disease.
					
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