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 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:
15.49 – 15.53 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, Godzik A, Reed JC (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, Jung YK (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, 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. 
  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, Alnemri ES, Salvesen GS, Reed JC (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, Vincenz C, Ward PA (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, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (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, Tian L, Frank S, Youle RJ, Nelson DL, Notarangelo LD, Vezzoni P, Fearnhead HO, Duckett CS (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