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; CASPASE-9c; 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:
15.82 – 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 NLRP1,[3][4] XIAP,[5][6][7][8] Baculoviral IAP repeat-containing protein 3,[7] BIRC2,[7] APAF1[3][9][10][11][12] and Caspase 8.[13][14]

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, Z L; Pio F; Xie Z; Welsh K; Krajewska M; Krajewski S; Godzik A; Reed J C (March 2001). "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". J. Biol. Chem. (United States) 276 (12): 9239–45. doi:10.1074/jbc.M006309200. ISSN 0021-9258. PMID 11113115. 
  4. ^ Hlaing, T; Guo R F; Dilley K A; Loussia J M; Morrish T A; Shi M M; Vincenz C; Ward P A (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. (United States) 276 (12): 9230–8. doi:10.1074/jbc.M009853200. ISSN 0021-9258. PMID 11076957. 
  5. ^ Rual, Jean-François; Venkatesan Kavitha, Hao Tong, Hirozane-Kishikawa Tomoko, Dricot Amélie, Li Ning, Berriz Gabriel F, Gibbons Francis D, Dreze Matija, Ayivi-Guedehoussou Nono, Klitgord Niels, Simon Christophe, Boxem Mike, Milstein Stuart, Rosenberg Jennifer, Goldberg Debra S, Zhang Lan V, Wong Sharyl L, Franklin Giovanni, Li Siming, Albala Joanna S, Lim Janghoo, Fraughton Carlene, Llamosas Estelle, Cevik Sebiha, Bex Camille, Lamesch Philippe, Sikorski Robert S, Vandenhaute Jean, Zoghbi Huda Y, Smolyar Alex, Bosak Stephanie, Sequerra Reynaldo, Doucette-Stamm Lynn, Cusick Michael E, Hill David E, Roth Frederick P, Vidal Marc (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature (England) 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. 
  6. ^ Davoodi, Jamshid; Lin Lily; Kelly John; Liston Peter; MacKenzie Alexander E (September 2004). "Neuronal apoptosis-inhibitory protein does not interact with Smac and requires ATP to bind caspase-9". J. Biol. Chem. (United States) 279 (39): 40622–8. doi:10.1074/jbc.M405963200. ISSN 0021-9258. PMID 15280366. 
  7. ^ a b c Deveraux, Q L; Roy N; Stennicke H R; Van Arsdale T; Zhou Q; Srinivasula S M; Alnemri E S; Salvesen G S; Reed J C (April 1998). "IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases". EMBO J. (ENGLAND) 17 (8): 2215–23. doi:10.1093/emboj/17.8.2215. ISSN 0261-4189. PMC 1170566. PMID 9545235. 
  8. ^ Richter, B W; Mir S S, Eiben L J, Lewis J, Reffey S B, Frattini A, Tian L, Frank S, Youle R J, Nelson D L, Notarangelo L D, Vezzoni P, Fearnhead H O, Duckett C S (July 2001). "Molecular Cloning of ILP-2, a Novel Member of the Inhibitor of Apoptosis Protein Family". Mol. Cell. Biol. (United States) 21 (13): 4292–301. doi:10.1128/MCB.21.13.4292-4301.2001. ISSN 0270-7306. PMC 87089. PMID 11390657. 
  9. ^ Cho, Dong-Hyung; Hong Yeon-Mi; Lee Ho-June; Woo Ha-Na; Pyo Jong-Ok; Mak Tak W; Jung Yong-Keun (September 2004). "Induced inhibition of ischemic/hypoxic injury by APIP, a novel Apaf-1-interacting protein". J. Biol. Chem. (United States) 279 (38): 39942–50. doi:10.1074/jbc.M405747200. ISSN 0021-9258. PMID 15262985. 
  10. ^ Li, P; Nijhawan D; Budihardjo I; Srinivasula S M; Ahmad M; Alnemri E S; Wang X (November 1997). "Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade". Cell (UNITED STATES) 91 (4): 479–89. doi:10.1016/S0092-8674(00)80434-1. ISSN 0092-8674. PMID 9390557. 
  11. ^ Hu, Y; Benedict M A; 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. (UNITED STATES) 95 (8): 4386–91. doi:10.1073/pnas.95.8.4386. ISSN 0027-8424. PMC 22498. PMID 9539746. 
  12. ^ Pan, G; O'Rourke K; Dixit V M (March 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. (UNITED STATES) 273 (10): 5841–5. doi:10.1074/jbc.273.10.5841. ISSN 0021-9258. PMID 9488720. 
  13. ^ Guo, Yin; Srinivasula Srinivasa M, Druilhe Anne, Fernandes-Alnemri Teresa, Alnemri Emad S (April 2002). "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. (United States) 277 (16): 13430–7. doi:10.1074/jbc.M108029200. ISSN 0021-9258. PMID 11832478. 
  14. ^ Srinivasula, S M; Ahmad M; Fernandes-Alnemri T; Litwack G; Alnemri E S (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. (UNITED STATES) 93 (25): 14486–91. doi:10.1073/pnas.93.25.14486. ISSN 0027-8424. PMC 26159. PMID 8962078. 

External links[edit]

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

Further reading[edit]