caspase 6

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. 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.{{cite journal | vauthors = Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD | title = Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation | journal = EMBO Rep | volume = 11 | issue = 11 | pages = 841–7 | date = Nov 2010 | pmid = 20890311 | pmc = 2966951 | doi = 10.1038/embor.2010.141 }} Alternative splicing of this gene results in two transcript variants that encode different isoforms.{{cite web | title = Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=839}}

Caspase-6 plays a role in the early immune response via de-repression. It reduces the expression of the immunosuppressant cytokine interleukin-10 and cleaves the macrophage suppressing IRAK-M.

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.

Caspase 6 has been shown to interact with Caspase 8.{{cite journal | vauthors = Cowling V, Downward J | title = Caspase-6 is the direct activator of caspase-8 in the cytochrome c-induced apoptosis pathway: absolute requirement for removal of caspase-6 prodomain | journal = Cell Death Differ. | volume = 9 | issue = 10 | pages = 1046–56 | date = Oct 2002 | pmid = 12232792 | doi = 10.1038/sj.cdd.4401065 | doi-access = free }}{{cite journal | vauthors = Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES | title = Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria | journal = J. Biol. Chem. | volume = 277 | issue = 16 | pages = 13430–7 | date = Apr 2002 | pmid = 11832478 | doi = 10.1074/jbc.M108029200 | doi-access = free }}{{cite journal | vauthors = Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 25 | pages = 14486–91 | date = Dec 1996 | pmid = 8962078 | pmc = 26159 | doi = 10.1073/pnas.93.25.14486 | bibcode = 1996PNAS...9314486S | doi-access = free }}

• The Proteolysis Map
• Caspase

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• {{cite journal|year = 1995|title = CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme|journal = J. Biol. Chem.|volume = 269|issue = 49|pages = 30761–4|pmid = 7983002|vauthors = Fernandes-Alnemri T, Litwack G, Alnemri ES|doi = 10.1016/S0021-9258(18)47344-9|doi-access = free}}
• {{cite journal|year = 1996|title = 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|journal = Proc. Natl. Acad. Sci. U.S.A.|volume = 93|issue = 16|pages = 8395–400|doi = 10.1073/pnas.93.16.8395|pmc = 38682|pmid = 8710882|vauthors = Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC|bibcode = 1996PNAS...93.8395T|doi-access = free}}
• {{cite journal|year = 1997|title = Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3|journal = Genomics|volume = 36|issue = 2|pages = 362–5|doi = 10.1006/geno.1996.0476|pmid = 8812467|vauthors = Bullrich F, Fernandes-Alnemri T, Litwack G, Alnemri ES, Croce CM}}
• {{cite journal|year = 1996|title = The Ced-3/interleukin 1beta converting enzyme-like homolog Mch6 and the lamin-cleaving enzyme Mch2alpha are substrates for the apoptotic mediator CPP32|journal = J. Biol. Chem.|volume = 271|issue = 43|pages = 27099–106|doi = 10.1074/jbc.271.43.27099|pmid = 8900201|vauthors = Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES|doi-access = free}}
• {{cite journal|year = 1997|title = 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|journal = Proc. Natl. Acad. Sci. U.S.A.|volume = 93|issue = 25|pages = 14486–91|doi = 10.1073/pnas.93.25.14486|pmc = 26159|pmid = 8962078|vauthors = Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES| bibcode=1996PNAS...9314486S |doi-access = free}}
• {{cite journal|year = 1997|title = Lamin proteolysis facilitates nuclear events during apoptosis|journal = J. Cell Biol.|volume = 135|issue = 6 Pt 1|pages = 1441–55|doi = 10.1083/jcb.135.6.1441|pmc = 2133948|pmid = 8978814|vauthors = Rao L, Perez D, White E}}
• {{cite journal|year = 1998|title = Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease|journal = Science|volume = 277|issue = 5324|pages = 373–6|doi = 10.1126/science.277.5324.373|pmid = 9219695|vauthors = Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE|citeseerx=10.1.1.1025.8052}}
• {{cite journal|year = 1997|title = FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis|journal = J. Biol. Chem.|volume = 272|issue = 30|pages = 18542–5|doi = 10.1074/jbc.272.30.18542|pmid = 9228018|vauthors = Srinivasula SM, Ahmad M, Ottilie S, Bullrich F, Banks S, Wang Y, Fernandes-Alnemri T, Croce CM, Litwack G, Tomaselli KJ, Armstrong RC, Alnemri ES|doi-access = free}}
• {{cite journal|year = 1997|title = Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis|journal = J. Cell Biol.|volume = 138|issue = 6|pages = 1379–94|doi = 10.1083/jcb.138.6.1379|pmc = 2132555|pmid = 9298992|vauthors = Caulín C, Salvesen GS, Oshima RG}}
• {{cite journal|year = 1998|title = Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis|journal = J. Exp. Med.|volume = 187|issue = 4|pages = 587–600|doi = 10.1084/jem.187.4.587|pmc = 2212161|pmid = 9463409|vauthors = Hirata H, Takahashi A, Kobayashi S, Yonehara S, Sawai H, Okazaki T, Yamamoto K, Sasada M}}
• {{cite journal|year = 1998|title = Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis|journal = J. Biol. Chem.|volume = 273|issue = 22|pages = 13524–30|doi = 10.1074/jbc.273.22.13524|pmid = 9593687|vauthors = Harvey KF, Harvey NL, Michael JM, Parasivam G, Waterhouse N, Alnemri ES, Watters D, Kumar S|doi-access = free}}
• {{cite journal|year = 1999|title = The 72-kDa component of signal recognition particle is cleaved during apoptosis|journal = J. Biol. Chem.|volume = 273|issue = 52|pages = 35362–70|doi = 10.1074/jbc.273.52.35362|pmid = 9857079|vauthors = Utz PJ, Hottelet M, Le TM, Kim SJ, Geiger ME, van Venrooij WJ, Anderson P|doi-access = free}}
• {{cite journal|year = 1999|title = Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis|journal = J. Biol. Chem.|volume = 274|issue = 7|pages = 4335–40|doi = 10.1074/jbc.274.7.4335|pmid = 9933635|vauthors = Samejima K, Svingen PA, Basi GS, Kottke T, Mesner PW, Stewart L, Durrieu F, Poirier GG, Alnemri ES, Champoux JJ, Kaufmann SH, Earnshaw WC|doi-access = free}}
• {{cite journal|year = 1999|title = Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis|journal = Proc. Natl. Acad. Sci. U.S.A.|volume = 96|issue = 4|pages = 1391–6|doi = 10.1073/pnas.96.4.1391|pmc = 15473|pmid = 9990034|vauthors = Walter J, Schindzielorz A, Grünberg J, Haass C|bibcode = 1999PNAS...96.1391W|doi-access = free}}
• {{cite journal|year = 1999|title = Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases|journal = FEBS Lett.|volume = 445|issue = 1|pages = 149–54|doi = 10.1016/S0014-5793(99)00108-8|pmid = 10069390|vauthors = van de Craen M, de Jonghe C, van den Brande I, Declercq W, van Gassen G, van Criekinge W, Vanderhoeven I, Fiers W, van Broeckhoven C, Hendriks L, Vandenabeele P|hdl = 10067/238040151162165141|s2cid = 31218178| url=https://repository.uantwerpen.be/docman/irua/8538a1/5202.pdf |hdl-access = free}}
• {{cite journal|year = 1999|title = Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis|journal = EMBO J.|volume = 18|issue = 8|pages = 2049–56|doi = 10.1093/emboj/18.8.2049|pmc = 1171289|pmid = 10205159|vauthors = Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson DW}}

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• The MEROPS online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=C14.005 C14.005] {{Webarchive|url=https://web.archive.org/web/20080205175111/http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=C14.005 |date=2008-02-05 }}
• {{PDBe-KB2|P55212|Human Caspase-6}}

{{Cysteine proteases}}

{{Enzymes}}

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Category:EC 3.4.22

Category:Caspases