CASP9

This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants.

Caspase 9

CASP9; APAF-3; APAF3; ICE-LAP6; MCH6; PPP1R56; caspase-9

Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).
Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9.

Activation of cysteine-type endopeptidase activity involved in apoptotic process Source: GO_Central
Activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c Source: Reactome
Apoptotic process Source: UniProtKB
Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to UV Source: UniProtKB
Extrinsic apoptotic signaling pathway in absence of ligand Source: Reactome
Intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
Platelet formation Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Regulation of response to DNA damage stimulus Source: UniProtKB
Signal transduction in response to DNA damage Source: UniProtKB

Apoptosome; Cytosol; Cytoplasm; Protein-containing complex

Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. Caspase-8 and -10 can also be involved in these processing events.
Phosphorylated at Thr-125 by MAPK1/ERK2. Phosphorylation at Thr-125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation. Phosphorylation on Tyr-153 by ABL1/c-Abl; occurs in the response of cells to DNA damage.