Caspase 8

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Caspase 8, apoptosis-related cysteine peptidase
Protein CASP8 PDB 1f9e.png
PDB rendering based on 1f9e.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CASP8 ; ALPS2B; CAP4; Casp-8; FLICE; MACH; MCH5
External IDs OMIM601763 MGI1261423 HomoloGene7657 ChEMBL: 3776 GeneCards: CASP8 Gene
EC number 3.4.22.61
RNA expression pattern
PBB GE CASP8 213373 s at tn.png
PBB GE CASP8 207686 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 841 12370
Ensembl ENSG00000064012 ENSMUSG00000026029
UniProt Q14790 O89110
RefSeq (mRNA) NM_001080124 NM_001080126
RefSeq (protein) NP_001073593 NP_001073595
Location (UCSC) Chr 2:
202.1 – 202.15 Mb
Chr 1:
58.8 – 58.85 Mb
PubMed search [1] [2]

Caspase-8 is a caspase protein, encoded by the CASP8 gene. It most likely acts upon caspase-3. CASP8 orthologs [1] have been identified in numerous mammals for which complete genome data are available. These unique orthologs are also present in birds.

Description[edit]

The CASP8 gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes composed of a prodomain, a large protease subunit, and a small protease subunit. Activation of caspases requires proteolytic processing at conserved internal aspartic residues to generate a heterodimeric enzyme consisting of the large and small subunits. This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. The N-terminal FADD-like death effector domain of this protein suggests that it may interact with Fas-interacting protein FADD. This protein was detected in the insoluble fraction of the affected brain region from Huntington disease patients but not in those from normal controls, which implicated the role in neurodegenerative diseases. Many alternatively spliced transcript variants encoding different isoforms have been described, although not all variants have had their full-length sequences determined.[2]

Interactions[edit]

Caspase-8 has been shown to interact with:

Additional Photos[edit]

Signaling pathway of TNF-R1. Dashed grey lines represent multiple steps
Overview of signal transduction pathways involved in apoptosis.

See also[edit]

References[edit]

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  4. ^ a b c d e f Gajate C, Mollinedo F (March 2005). "Cytoskeleton-mediated death receptor and ligand concentration in lipid rafts forms apoptosis-promoting clusters in cancer chemotherapy". J. Biol. Chem. 280 (12): 11641–7. doi:10.1074/jbc.M411781200. PMID 15659383. 
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  15. ^ Cowling V, Downward J (October 2002). "Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain". Cell Death Differ. 9 (10): 1046–56. doi:10.1038/sj.cdd.4401065. PMID 12232792. 
  16. ^ Zhan Y, Hegde R, Srinivasula SM, Fernandes-Alnemri T, Alnemri ES (April 2002). "Death effector domain-containing proteins DEDD and FLAME-3 form nuclear complexes with the TFIIIC102 subunit of human transcription factor IIIC". Cell Death Differ. 9 (4): 439–47. doi:10.1038/sj/cdd/4401038. PMID 11965497. 
  17. ^ Alcivar A, Hu S, Tang J, Yang X (January 2003). "DEDD and DEDD2 associate with caspase-8/10 and signal cell death". Oncogene 22 (2): 291–7. doi:10.1038/sj.onc.1206099. PMID 12527898. 
  18. ^ Stegh AH, Schickling O, Ehret A, Scaffidi C, Peterhänsel C, Hofmann TG, Grummt I, Krammer PH, Peter ME (October 1998). "DEDD, a novel death effector domain-containing protein, targeted to the nucleolus". EMBO J. 17 (20): 5974–86. doi:10.1093/emboj/17.20.5974. PMC 1170924. PMID 9774341. 
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  21. ^ Boldin MP, Goncharov TM, Goltsev YV, Wallach D (June 1996). "Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death". Cell 85 (6): 803–15. PMID 8681376. 
  22. ^ Thomas LR, Stillman DJ, Thorburn A (September 2002). "Regulation of Fas-associated death domain interactions by the death effector domain identified by a modified reverse two-hybrid screen". J. Biol. Chem. 277 (37): 34343–8. doi:10.1074/jbc.M204169200. PMID 12107169. 
  23. ^ a b MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES (October 1997). "Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL". J. Biol. Chem. 272 (41): 25417–20. PMID 9325248. 
  24. ^ Gervais FG, Singaraja R, Xanthoudakis S, Gutekunst CA, Leavitt BR, Metzler M, Hackam AS, Tam J, Vaillancourt JP, Houtzager V, Rasper DM, Roy S, Hayden MR, Nicholson DW (February 2002). "Recruitment and activation of caspase-8 by the Huntingtin-interacting protein Hip-1 and a novel partner Hippi". Nat. Cell Biol. 4 (2): 95–105. doi:10.1038/ncb735. PMID 11788820. 
  25. ^ Koseki T, Inohara N, Chen S, Núñez G (April 1998). "ARC, an inhibitor of apoptosis expressed in skeletal muscle and heart that interacts selectively with caspases". Proc. Natl. Acad. Sci. U.S.A. 95 (9): 5156–60. PMC 20230. PMID 9560245. 
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Further reading[edit]

External links[edit]