Caspase 6: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Caspase-6''' is an [[enzyme]] that in humans is encoded by the ''CASP6'' [[gene]].<ref name="pmid8780721">{{cite journal | vauthors = Tiso N, Pallavicini A, Muraro T, Zimbello R, Apolloni E, Valle G, Lanfranchi G, Danieli GA | title = Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis | journal = Biochem Biophys Res Commun | volume = 225 | issue = 3 | pages = 983–9 | date = Oct 1996 | pmid = 8780721 | pmc =  | doi = 10.1006/bbrc.1996.1282 }}</ref><ref name="pmid7796396">{{cite journal | vauthors = Fernandes-Alnemri T, Litwack G, Alnemri ES | title = Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family | journal = Cancer Res | volume = 55 | issue = 13 | pages = 2737–42 | date = Aug 1995 | pmid = 7796396 | pmc =  | doi =  }}</ref>
| update_page = yes
''CASP6'' [[orthologs]] <ref name="OrthoMaM">{{cite web | title = OrthoMaM phylogenetic marker: CASP6 coding sequence | url = http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000138794_CASP6.xml  }}</ref> have been identified in numerous [[mammals]] for which complete genome data are available. Unique orthologs are also present in [[birds]], [[lizards]], [[lissamphibian]]s, and [[teleosts]]. Caspase-6 has known functions in [[apoptosis]]<ref name=":0">{{Cite journal|last=Cohen|first=Gerald M.|date=1997-08-15|title=Caspases: the executioners of apoptosis|url=http://www.biochemj.org/content/326/1/1|journal=Biochemical Journal|language=en|volume=326|issue=1|pages=1–16|doi=10.1042/bj3260001|issn=0264-6021|pmid=9337844}}</ref>, early [[Immune system|immune response]]<ref name=":1">{{Cite journal|last=Bartel|first=Alexander|last2=Göhler|first2=André|last3=Hopf|first3=Verena|last4=Breitbach|first4=Katrin|date=2017-07-07|title=Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines|url=http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180203|journal=PLOS ONE|volume=12|issue=7|pages=e0180203|doi=10.1371/journal.pone.0180203|issn=1932-6203}}</ref><ref name=":2">{{Cite journal|last=Kobayashi|first=Hiroshi|last2=Nolan|first2=Anna|last3=Naveed|first3=Bushra|last4=Hoshino|first4=Yoshihiko|last5=Segal|first5=Leopoldo N.|last6=Fujita|first6=Yoko|last7=Rom|first7=William N.|last8=Weiden|first8=Michael D.|date=2011-01-01|title=Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M|url=http://www.jimmunol.org/content/186/1/403|journal=The Journal of Immunology|language=en|volume=186|issue=1|pages=403–410|doi=10.4049/jimmunol.1001906|issn=0022-1767|pmc=3151149|pmid=21098228}}</ref> and [[Neurodegeneration|neurodegenration]] in [[Huntington's disease|Huntington's]] and [[Alzheimer's disease]].<ref name=":3">{{Cite journal|last=Graham|first=Rona K.|last2=Ehrnhoefer|first2=Dagmar E.|last3=Hayden|first3=Michael R.|date=2011-12-01|title=Caspase-6 and neurodegeneration|url=http://www.cell.com/trends/neurosciences/abstract/S0166-2236(11)00154-8|journal=Trends in Neurosciences|language=English|volume=34|issue=12|pages=646–656|doi=10.1016/j.tins.2011.09.001|issn=0166-2236|pmid=22018804}}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Caspase 6, apoptosis-related cysteine peptidase
| HGNCid = 1507
| Symbol = CASP6
| AltSymbols =; MCH2
| OMIM = 601532
| ECnumber = 
| Homologene = 37455
| MGIid = 1312921
| GeneAtlas_image1 = PBB_GE_CASP6_209790_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_CASP6_211464_x_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008234 |text = cysteine-type peptidase activity}} {{GNF_GO|id=GO:0030693 |text = caspase activity}}
| Component =
| Process = {{GNF_GO|id=GO:0006508 |text = proteolysis}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0006917 |text = induction of apoptosis}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 839
    | Hs_Ensembl = ENSG00000138794
    | Hs_RefseqProtein = NP_001217
    | Hs_RefseqmRNA = NM_001226
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 110829234
    | Hs_GenLoc_end = 110844078
    | Hs_Uniprot = P55212
    | Mm_EntrezGene = 12368
    | Mm_Ensembl = ENSMUSG00000027997
    | Mm_RefseqmRNA = NM_009811
    | Mm_RefseqProtein = NP_033941
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 3
    | Mm_GenLoc_start = 129897501
    | Mm_GenLoc_end = 129905595
    | Mm_Uniprot = Q3TPJ9
  }}
}}
'''Caspase 6, apoptosis-related cysteine peptidase''', also known as '''CASP6''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a protein that is a member of the [[Cysteine protease|cysteine]]-[[aspartic acid]] [[protease]] ([[caspase]]) family. Sequential activation of caspases plays a central role in the execution-phase of cell [[apoptosis]].<ref name=":0" /> Caspases exist as inactive [[proenzyme]]s that undergo [[proteolysis|proteolytic]] processing at conserved aspartic residues to produce two subunits, large and small, that [[protein dimer|dimer]]ize to form the active enzyme. This protein is processed by [[caspase 7|caspases 7]], [[caspase 8|8]] and [[caspase 10|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.<ref name="pmid20890311">{{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 }}</ref> [[Alternative splicing]] of this gene results in two transcript variants that encode different isoforms.<ref>{{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| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = This gene encodes a protein which is a member of the [[Cysteine protease|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 [[proenzyme]]s which undergo [[proteolysis|proteolytic]] processing at conserved aspartic residues to produce two subunits, large and small, that [[dimer]]ize to form the active enzyme. This protein is processed by [[caspase 7|caspases 7]], [[caspase 8|8]] and [[caspase 10|10]], and is thought to function as a downstream enzyme in the caspase activation cascade. [[Alternative splicing]] of this gene results in two transcript variants that encode different isoforms.<ref>{{cite web | title = Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=839| accessdate = }}</ref>
}}


==References==
Caspase-6 plays a role in the early immune response via de-repression. It reduces the expression of the immunosuppressant cytokine [[Interleukin 10|interleukin-10]]<ref name=":1" /> and cleaves the macrophage suppressing [[IRAK3|IRAK-M]].<ref name=":2" />
{{reflist|2}}
 
==Further reading==
With respect to [[neurodegeneration]], caspase-6 cleaves [[Huntingtin|HTT]] in [[Huntington's]] and [[Amyloid precursor protein|APP]] in [[Alzheimer's disease]]. Resulting in both cases in [[protein aggregation]] of the fragments.<ref name=":3" />
{{refbegin | 2}}
 
{{PBB_Further_reading
== Interactions ==
| citations =  
 
*{{cite journal | author=Cohen GM |title=Caspases: the executioners of apoptosis. |journal=Biochem. J. |volume=326 ( Pt 1) |issue= |pages= 1-16 |year= 1997 |pmid= 9337844 |doi= }}
Caspase 6 has been shown to [[Protein-protein interaction|interact]] with [[Caspase 8]].<ref name=pmid12232792>{{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 }}</ref><ref name=pmid11832478>{{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 }}</ref><ref name=pmid8962078>{{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 = [[PNAS|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 }}</ref>
*{{cite journal | author=Fernandes-Alnemri T, Litwack G, Alnemri ES |title=Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. |journal=Cancer Res. |volume=55 |issue= 13 |pages= 2737-42 |year= 1995 |pmid= 7796396 |doi= }}
 
*{{cite journal | author=Fernandes-Alnemri T, Litwack G, Alnemri ES |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 |year= 1995 |pmid= 7983002 |doi= }}
== See also ==
*{{cite journal  | author=Takahashi A, Alnemri ES, Lazebnik YA, ''et al.'' |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 |year= 1996 |pmid= 8710882 |doi= }}
* [[The Proteolysis Map]]
*{{cite journal | author=Tiso N, Pallavicini A, Muraro T, ''et al.'' |title=Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis. |journal=Biochem. Biophys. Res. Commun. |volume=225 |issue= 3 |pages= 983-9 |year= 1996 |pmid= 8780721 |doi= 10.1006/bbrc.1996.1282 }}
* [[Caspase]]
*{{cite journal  | author=Bullrich F, Fernandes-Alnemri T, Litwack G, ''et al.'' |title=Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3. |journal=Genomics |volume=36 |issue= 2 |pages= 362-5 |year= 1997 |pmid= 8812467 |doi= 10.1006/geno.1996.0476 }}
 
*{{cite journal  | author=Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, ''et al.'' |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 |year= 1996 |pmid= 8900201 |doi= }}
== References ==
*{{cite journal | author=Srinivasula SM, Ahmad M, Fernandes-Alnemri T, ''et al.'' |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 |year= 1997 |pmid= 8962078 |doi= }}
{{reflist}}
*{{cite journal  | author=Rao L, Perez D, White E |title=Lamin proteolysis facilitates nuclear events during apoptosis. |journal=J. Cell Biol. |volume=135 |issue= 6 Pt 1 |pages= 1441-55 |year= 1997 |pmid= 8978814 |doi=  }}
{{Clear}}
*{{cite journal  | author=Kim TW, Pettingell WH, Jung YK, ''et al.'' |title=Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. |journal=Science |volume=277 |issue= 5324 |pages= 373-6 |year= 1998 |pmid= 9219695 |doi= }}
 
*{{cite journal  | author=Srinivasula SM, Ahmad M, Ottilie S, ''et al.'' |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 |year= 1997 |pmid= 9228018 |doi= }}
== Further reading ==
*{{cite journal | author=Caulín C, Salvesen GS, Oshima RG |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 |year= 1997 |pmid= 9298992 |doi= }}
{{refbegin|35em}}
*{{cite journal  | author=Hirata H, Takahashi A, Kobayashi S, ''et al.'' |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 |year= 1998 |pmid= 9463409 |doi= }}
* {{cite journal|last=|first=|date=|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|url=|journal = J. Biol. Chem.|volume = 269|issue = 49|pages = 30761–4|doi =|pmid = 7983002|via=|vauthors = Fernandes-Alnemri T, Litwack G, Alnemri ES}}
*{{cite journal  | author=Harvey KF, Harvey NL, Michael JM, ''et al.'' |title=Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis. |journal=J. Biol. Chem. |volume=273 |issue= 22 |pages= 13524-30 |year= 1998 |pmid= 9593687 |doi=  }}
* {{cite journal|last=|first=|date=|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|url=|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|via=|vauthors = Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC}}
*{{cite journal | author=Utz PJ, Hottelet M, Le TM, ''et al.'' |title=The 72-kDa component of signal recognition particle is cleaved during apoptosis. |journal=J. Biol. Chem. |volume=273 |issue= 52 |pages= 35362-70 |year= 1999 |pmid= 9857079 |doi=  }}
* {{cite journal|last=|first=|date=|year = 1997|title = Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3|url=|journal = Genomics|volume = 36|issue = 2|pages = 362–5|doi = 10.1006/geno.1996.0476|pmid = 8812467|via=|vauthors = Bullrich F, Fernandes-Alnemri T, Litwack G, Alnemri ES, Croce CM}}
*{{cite journal | author=Samejima K, Svingen PA, Basi GS, ''et al.'' |title=Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis. |journal=J. Biol. Chem. |volume=274 |issue= 7 |pages= 4335-40 |year= 1999 |pmid= 9933635 |doi= }}
* {{cite journal|last=|first=|date=|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|url=|journal = J. Biol. Chem.|volume = 271|issue = 43|pages = 27099–106|doi = 10.1074/jbc.271.43.27099|pmid = 8900201|via=|vauthors = Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES}}
*{{cite journal  | author=Walter J, Schindzielorz A, Grünberg J, Haass C |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 |year= 1999 |pmid= 9990034 |doi=  }}
* {{cite journal|last=|first=|date=|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|url=|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|via=|vauthors = Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES}}
*{{cite journal | author=van de Craen M, de Jonghe C, van den Brande I, ''et al.'' |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 |year= 1999 |pmid= 10069390 |doi= }}
* {{cite journal|last=|first=|date=|year = 1997|title = Lamin proteolysis facilitates nuclear events during apoptosis|url=|journal = J. Cell Biol.|volume = 135|issue = 6 Pt 1|pages = 1441–55|doi = 10.1083/jcb.135.6.1441|pmc = 2133948|pmid = 8978814|via=|vauthors = Rao L, Perez D, White E}}
*{{cite journal  | author=Xanthoudakis S, Roy S, Rasper D, ''et al.'' |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 |year= 1999 |pmid= 10205159 |doi= 10.1093/emboj/18.8.2049 }}
* {{cite journal|last=|first=|date=|year = 1998|title = Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease|url=|journal = Science|volume = 277|issue = 5324|pages = 373–6|doi = 10.1126/science.277.5324.373|pmid = 9219695|via=|vauthors = Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE}}
}}
* {{cite journal|last=|first=|date=|year = 1997|title = FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis|url=|journal = J. Biol. Chem.|volume = 272|issue = 30|pages = 18542–5|doi = 10.1074/jbc.272.30.18542|pmid = 9228018|via=|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}}
* {{cite journal|last=|first=|date=|year = 1997|title = Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis|url=|journal = J. Cell Biol.|volume = 138|issue = 6|pages = 1379–94|doi = 10.1083/jcb.138.6.1379|pmc = 2132555|pmid = 9298992|via=|vauthors = Caulín C, Salvesen GS, Oshima RG}}
* {{cite journal|last=|first=|date=|year = 1998|title = Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis|url=|journal = J. Exp. Med.|volume = 187|issue = 4|pages = 587–600|doi = 10.1084/jem.187.4.587|pmc = 2212161|pmid = 9463409|via=|vauthors = Hirata H, Takahashi A, Kobayashi S, Yonehara S, Sawai H, Okazaki T, Yamamoto K, Sasada M}}
* {{cite journal|last=|first=|date=|year = 1998|title = Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis|url=|journal = J. Biol. Chem.|volume = 273|issue = 22|pages = 13524–30|doi = 10.1074/jbc.273.22.13524|pmid = 9593687|via=|vauthors = Harvey KF, Harvey NL, Michael JM, Parasivam G, Waterhouse N, Alnemri ES, Watters D, Kumar S}}
* {{cite journal|last=|first=|date=|year = 1999|title = The 72-kDa component of signal recognition particle is cleaved during apoptosis|url=|journal = J. Biol. Chem.|volume = 273|issue = 52|pages = 35362–70|doi = 10.1074/jbc.273.52.35362|pmid = 9857079|via=|vauthors = Utz PJ, Hottelet M, Le TM, Kim SJ, Geiger ME, van Venrooij WJ, Anderson P}}
* {{cite journal|last=|first=|date=|year = 1999|title = Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis|url=|journal = J. Biol. Chem.|volume = 274|issue = 7|pages = 4335–40|doi = 10.1074/jbc.274.7.4335|pmid = 9933635|via=|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}}
* {{cite journal|last=|first=|date=|year = 1999|title = Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis|url=|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|via=|vauthors = Walter J, Schindzielorz A, Grünberg J, Haass C}}
* {{cite journal|last=|first=|date=|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|url=|journal = FEBS Lett.|volume = 445|issue = 1|pages = 149–54|doi = 10.1016/S0014-5793(99)00108-8|pmid = 10069390|via=|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}}
* {{cite journal|last=|first=|date=|year = 1999|title = Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis|url=|journal = EMBO J.|volume = 18|issue = 8|pages = 2049–56|doi = 10.1093/emboj/18.8.2049|pmc = 1171289|pmid = 10205159|via=|vauthors = Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson DW}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=C14.005 C14.005]
 
{{Cysteine proteases}}
{{Enzymes}}
{{Portal bar|Molecular and Cellular Biology|border=no}}
 
[[Category:EC 3.4.22]]
[[Category:Caspases]]

Revision as of 11:38, 30 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Wikidata
View/Edit Human

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 neurodegenration 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

  1. ↑ Tiso N, Pallavicini A, Muraro T, Zimbello R, Apolloni E, Valle G, Lanfranchi G, Danieli GA (Oct 1996). "Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis". Biochem Biophys Res Commun. 225 (3): 983–9. doi:10.1006/bbrc.1996.1282. PMID 8780721.
  2. ↑ Fernandes-Alnemri T, Litwack G, Alnemri ES (Aug 1995). "Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family". Cancer Res. 55 (13): 2737–42. PMID 7796396.
  3. ↑ "OrthoMaM phylogenetic marker: CASP6 coding sequence".
  4. ↑ 4.0 4.1 Cohen, Gerald M. (1997-08-15). "Caspases: the executioners of apoptosis". Biochemical Journal. 326 (1): 1–16. doi:10.1042/bj3260001. ISSN 0264-6021. PMID 9337844.
  5. ↑ 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.
  6. ↑ 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". The Journal of Immunology. 186 (1): 403–410. doi:10.4049/jimmunol.1001906. ISSN 0022-1767. PMC 3151149. PMID 21098228.
  7. ↑ 7.0 7.1 Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. (2011-12-01). "Caspase-6 and neurodegeneration". Trends in Neurosciences. 34 (12): 646–656. doi:10.1016/j.tins.2011.09.001. ISSN 0166-2236. PMID 22018804.
  8. ↑ Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD (Nov 2010). "Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation". EMBO Rep. 11 (11): 841–7. doi:10.1038/embor.2010.141. PMC 2966951. PMID 20890311.
  9. ↑ "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase".
  10. ↑ Cowling V, Downward J (Oct 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.
  11. ↑ Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES (Apr 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.
  12. ↑ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (Dec 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.

Further reading

External links

  • The MEROPS online database for peptidases and their inhibitors: C14.005
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