Caspase-9

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Caspase 9, apoptosis-related cysteine peptidase
Protein CASP9 PDB 1jxq.png
PDB rendering based on 1jxq.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CASP9 ; APAF-3; APAF3; ICE-LAP6; MCH6; PPP1R56
External IDs OMIM602234 MGI1277950 HomoloGene31024 IUPHAR: 1625 ChEMBL: 2273 GeneCards: CASP9 Gene
EC number 3.4.22.62
RNA expression pattern
PBB GE CASP9 203984 s at tn.png
PBB GE CASP9 210775 x at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 842 12371
Ensembl ENSG00000132906 ENSMUSG00000028914
UniProt P55211 Q8C3Q9
RefSeq (mRNA) NM_001229 NM_001277932
RefSeq (protein) NP_001220 NP_001264861
Location (UCSC) Chr 1:
15.82 – 15.85 Mb
Chr 4:
141.79 – 141.82 Mb
PubMed search [1] [2]

Caspase-9 is an initiator caspase,[1] encoded by the CASP9 gene. CASP9 orthologs [2] have been identified in all mammals for which complete genome data are available. Unique orthologs are also present in lizards, lissamphibians, and teleosts.

The aspartic acid specific protease caspase-9 has been linked to the mitochondrial death pathway. It is activated during programmed cell death (apoptosis). Induction of stress signaling pathways JNK/SAPK causes release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which in turn cleaves the pro-enzyme of caspase-9 into the active form.

Once initiated caspase-9 goes on to cleave procaspase-3 & procaspase-7, which cleave several cellular targets, including poly ADP ribose polymerase.

Interactions[edit]

Caspase-9 has been shown to interact with:

Overview of signal transduction pathways involved in apoptosis.

See also[edit]


References[edit]

  1. ^ Caspase 9
  2. ^ "OrthoMaM phylogenetic marker: CASP9 coding sequence". 
  3. ^ a b Chu ZL, Pio F, Xie Z, Welsh K, Krajewska M, Krajewski S et al. (March 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". J. Biol. Chem. 276 (12): 9239–45. doi:10.1074/jbc.M006309200. PMID 11113115. 
  4. ^ Cho DH, Hong YM, Lee HJ, Woo HN, Pyo JO, Mak TW et al. (September 2004). "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein". J. Biol. Chem. 279 (38): 39942–50. doi:10.1074/jbc.M405747200. PMID 15262985. 
  5. ^ Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES et al. (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. 
  6. ^ Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (April 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proc. Natl. Acad. Sci. U.S.A. 95 (8): 4386–91. doi:10.1073/pnas.95.8.4386. PMC 22498. PMID 9539746. 
  7. ^ Pan G, O'Rourke K, Dixit VM (March 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. 273 (10): 5841–5. doi:10.1074/jbc.273.10.5841. PMID 9488720. 
  8. ^ a b c Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM et al. (April 1998). "IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases". EMBO J. 17 (8): 2215–23. doi:10.1093/emboj/17.8.2215. PMC 1170566. PMID 9545235. 
  9. ^ Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (April 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. doi:10.1074/jbc.M108029200. PMID 11832478. 
  10. ^ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (December 1996). "Molecular ordering of the Fas-apoptotic pathway: the Fas/APO-1 protease Mch5 is a CrmA-inhibitable protease that activates multiple Ced-3/ICE-like cysteine proteases". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14486–91. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078. 
  11. ^ Hlaing T, Guo RF, Dilley KA, Loussia JM, Morrish TA, Shi MM et al. (March 2001). "Molecular cloning and characterization of DEFCAP-L and -S, two isoforms of a novel member of the mammalian Ced-4 family of apoptosis proteins". J. Biol. Chem. 276 (12): 9230–8. doi:10.1074/jbc.M009853200. PMID 11076957. 
  12. ^ Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  13. ^ Davoodi J, Lin L, Kelly J, Liston P, MacKenzie AE (September 2004). "Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9". J. Biol. Chem. 279 (39): 40622–8. doi:10.1074/jbc.M405963200. PMID 15280366. 
  14. ^ Richter BW, Mir SS, Eiben LJ, Lewis J, Reffey SB, Frattini A et al. (July 2001). "Molecular cloning of ILP-2, a novel member of the inhibitor of apoptosis protein family". Mol. Cell. Biol. 21 (13): 4292–301. doi:10.1128/MCB.21.13.4292-4301.2001. PMC 87089. PMID 11390657. 

Further reading[edit]

External links[edit]

  • The MEROPS online database for peptidases and their inhibitors: C14.010