CASP9
Description
The CASP9 (caspase 9) is a protein-coding gene located on chromosome 1.
Caspase-9 is an enzyme encoded by the CASP9 gene in humans. It is an initiator caspase crucial for the apoptotic pathway found in many tissues. Caspase-9 homologs have been identified in all mammals for which they are known to exist, including Mus musculus and Pan troglodytes. Caspase-9 belongs to a family of caspases, cysteine-aspartic proteases involved in apoptosis and cytokine signaling. Apoptotic signals trigger the release of cytochrome c from mitochondria and activation of Apaf-1 (apoptosome), which then cleaves the pro-enzyme of caspase-9 into the active dimer form. The enzyme is regulated by phosphorylation through an allosteric inhibitor, which inhibits dimerization and induces a conformational change. Proper caspase-9 function is essential for apoptosis, leading to normal development of the central nervous system. Caspase-9 also performs several additional cellular functions independent of its role in apoptosis. These nonapoptotic functions include regulation of necroptosis, cellular differentiation, innate immune response, sensory neuron maturation, mitochondrial homeostasis, corticospinal circuit organization, and ischemic vascular injury. Without proper caspase-9 function, abnormal tissue development can occur, leading to abnormal function, diseases, and premature death.
Caspase-9 is involved in the activation cascade of caspases, which are responsible for executing apoptosis. Binding of caspase-9 to Apaf-1 activates the protease, leading to the cleavage and activation of effector caspases like caspase-3 (CASP3) and caspase-7 (CASP7). Caspase-9 promotes DNA damage-induced apoptosis in a manner dependent on ABL1/c-Abl. It also proteolytically cleaves poly(ADP-ribose) polymerase (PARP).
CASP9 is also known as APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56.
