Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. It is an initiator caspase,[5] critical to the apoptotic pathway found in many tissues.[6] Caspase-9 homologs have been identified in all mammals for which they are known to exist, such as Mus musculus and Pan troglodytes.[7]
Caspase-9 belongs to a family of caspases, cysteine-aspartic proteases involved in apoptosis and cytokine signalling.[8] Apoptotic signals cause 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.[6] Regulation of this enzyme occurs through phosphorylation by an allosteric inhibitor, inhibiting dimerization and inducing a conformational change.[8]
Correct caspase-9 function is required for apoptosis, leading to the normal development of the central nervous system.[8] Caspase-9 has multiple additional cellular functions that are independent of its role in apoptosis. Nonapoptotic roles of caspase-9 include regulation of necroptosis, cellular differentiation, innate immune response, sensory neuron maturation, mitochondrial homeostasis, corticospinal circuit organization, and ischemic vascular injury. [9] Without correct function, abnormal tissue development can occur leading to abnormal function, diseases and premature death. [8] Caspase-9 loss-of-function mutations have been associated with immunodeficiency/lymphoproliferation, neural tube defects, and Li-Fraumeni-like syndrome. Increased caspase-9 activity is implicated in the progression of amyotrophic lateral sclerosis, retinal detachment, and slow-channel syndrome, as well as various other neurological, autoimmune, and cardiovascular disorders. [9]
Different protein isoforms of caspase-9 are produced due to alternative splicing.[10]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000132906 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028914 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Caspase 9
- ^ a b Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (November 1997). "Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade". Cell. 91 (4): 479–89. doi:10.1016/s0092-8674(00)80434-1. PMID 9390557. S2CID 14321446.
- ^ "HomoloGene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-12-01.
- ^ a b c d Kuida K (2000). "Caspase-9". The International Journal of Biochemistry & Cell Biology. 32 (2): 121–4. doi:10.1016/s1357-2725(99)00024-2. PMID 10687948.
- ^ a b Avrutsky MI, Troy CM (2021). "Caspase-9: A Multimodal Therapeutic Target With Diverse Cellular Expression in Human Disease". Frontiers in Pharmacology. 12: 701301. doi:10.3389/fphar.2021.701301. PMC 8299054. PMID 34305609.
- ^ "CASP9 caspase 9 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-11-30.