Biology:Caspase 6
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Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene.[1][2] CASP6 orthologs[3] have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis,[4] early immune response[5][6] and neurodegeneration in Huntington's and Alzheimer's disease.[7]
Function
This gene encodes a protein that is 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.[4] Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family.[8] Alternative splicing of this gene results in two transcript variants that encode different isoforms.[9]
Caspase-6 plays a role in the early immune response via de-repression. It reduces the expression of the immunosuppressant cytokine interleukin-10[5] and cleaves the macrophage suppressing IRAK-M.[6]
With respect to neurodegeneration, caspase-6 cleaves HTT in Huntington's and APP in Alzheimer's disease. Resulting in both cases in protein aggregation of the fragments.[7]
Interactions
Caspase 6 has been shown to interact with Caspase 8.[10][11][12]
See also
References
- ↑ "Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis". Biochem Biophys Res Commun 225 (3): 983–9. Oct 1996. doi:10.1006/bbrc.1996.1282. PMID 8780721.
- ↑ "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family". Cancer Res 55 (13): 2737–42. Aug 1995. PMID 7796396.
- ↑ "OrthoMaM phylogenetic marker: CASP6 coding sequence". http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000138794_CASP6.xml.
- ↑ 4.0 4.1 Cohen, Gerald M. (1997-08-15). "Caspases: the executioners of apoptosis" (in en). Biochemical Journal 326 (1): 1–16. doi:10.1042/bj3260001. ISSN 0264-6021. PMID 9337844.
- ↑ 5.0 5.1 Bartel, Alexander; Göhler, André; Hopf, Verena; Breitbach, Katrin (2017-07-07). "Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines". PLOS ONE 12 (7): e0180203. doi:10.1371/journal.pone.0180203. ISSN 1932-6203. PMID 28686630. Bibcode: 2017PLoSO..1280203B.
- ↑ 6.0 6.1 Kobayashi, Hiroshi; Nolan, Anna; Naveed, Bushra; Hoshino, Yoshihiko; Segal, Leopoldo N.; Fujita, Yoko; Rom, William N.; Weiden, Michael D. (2011-01-01). "Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M" (in en). The Journal of Immunology 186 (1): 403–410. doi:10.4049/jimmunol.1001906. ISSN 0022-1767. PMID 21098228.
- ↑ 7.0 7.1 Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. (2011-12-01). "Caspase-6 and neurodegeneration" (in en). Trends in Neurosciences 34 (12): 646–656. doi:10.1016/j.tins.2011.09.001. ISSN 0166-2236. PMID 22018804. http://www.cell.com/trends/neurosciences/abstract/S0166-2236(11)00154-8.
- ↑ "Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation". EMBO Rep 11 (11): 841–7. Nov 2010. doi:10.1038/embor.2010.141. PMID 20890311.
- ↑ "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=839.
- ↑ "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. Oct 2002. doi:10.1038/sj.cdd.4401065. PMID 12232792.
- ↑ "Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria". J. Biol. Chem. 277 (16): 13430–7. Apr 2002. doi:10.1074/jbc.M108029200. PMID 11832478.
- ↑ "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. Dec 1996. doi:10.1073/pnas.93.25.14486. PMID 8962078. Bibcode: 1996PNAS...9314486S.
Further reading
- "CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme". J. Biol. Chem. 269 (49): 30761–4. 1995. doi:10.1016/S0021-9258(18)47344-9. PMID 7983002.
- "Cleavage of lamin A by Mch2 alpha but not CPP32: multiple interleukin 1 beta-converting enzyme-related proteases with distinct substrate recognition properties are active in apoptosis". Proc. Natl. Acad. Sci. U.S.A. 93 (16): 8395–400. 1996. doi:10.1073/pnas.93.16.8395. PMID 8710882. Bibcode: 1996PNAS...93.8395T.
- "Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3". Genomics 36 (2): 362–5. 1997. doi:10.1006/geno.1996.0476. PMID 8812467.
- "The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32". J. Biol. Chem. 271 (43): 27099–106. 1996. doi:10.1074/jbc.271.43.27099. PMID 8900201.
- "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. 1997. doi:10.1073/pnas.93.25.14486. PMID 8962078. Bibcode: 1996PNAS...9314486S.
- "Lamin proteolysis facilitates nuclear events during apoptosis". J. Cell Biol. 135 (6 Pt 1): 1441–55. 1997. doi:10.1083/jcb.135.6.1441. PMID 8978814.
- "Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease". Science 277 (5324): 373–6. 1998. doi:10.1126/science.277.5324.373. PMID 9219695.
- "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542–5. 1997. doi:10.1074/jbc.272.30.18542. PMID 9228018.
- "Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis". J. Cell Biol. 138 (6): 1379–94. 1997. doi:10.1083/jcb.138.6.1379. PMID 9298992.
- "Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis". J. Exp. Med. 187 (4): 587–600. 1998. doi:10.1084/jem.187.4.587. PMID 9463409.
- "Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis". J. Biol. Chem. 273 (22): 13524–30. 1998. doi:10.1074/jbc.273.22.13524. PMID 9593687.
- "The 72-kDa component of signal recognition particle is cleaved during apoptosis". J. Biol. Chem. 273 (52): 35362–70. 1999. doi:10.1074/jbc.273.52.35362. PMID 9857079.
- "Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis". J. Biol. Chem. 274 (7): 4335–40. 1999. doi:10.1074/jbc.274.7.4335. PMID 9933635.
- "Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis". Proc. Natl. Acad. Sci. U.S.A. 96 (4): 1391–6. 1999. doi:10.1073/pnas.96.4.1391. PMID 9990034. Bibcode: 1999PNAS...96.1391W.
- "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases". FEBS Lett. 445 (1): 149–54. 1999. doi:10.1016/S0014-5793(99)00108-8. PMID 10069390. https://repository.uantwerpen.be/docman/irua/8538a1/5202.pdf.
- "Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis". EMBO J. 18 (8): 2049–56. 1999. doi:10.1093/emboj/18.8.2049. PMID 10205159.
External links
- The MEROPS online database for peptidases and their inhibitors: C14.005
- Overview of all the structural information available in the PDB for UniProt: P55212 (Human Caspase-6) at the PDBe-KB.
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