Kaspaza-6
Kaspaza-6 jest enzim koji je kod ljudi kodiran genom CASP6 sa hromosoma 4.[5][6] Ortolozi CASP6 [7] identificirani su kod brojnih sisara za koje su dostupni potpuni podaci o genomu. Jedinstveni ortolozi su također prisutni kod ptica, gušterova, Lissamphibia, i teleostea. Kaspaza-6 ima poznate funkcije u apoptozi,[8] ranom imunskom odgovoru[9][10] i neurodegeneracijama u Hantingtonovoj i Alzheimerovoj bolesti.[11]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 293 aminokiseline, a molekulska težina 33.310 Da.[9]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MSSASGLRRG | HPAGGEENMT | ETDAFYKREM | FDPAEKYKMD | HRRRGIALIF | ||||
NHERFFWHLT | LPERRGTCAD | RDNLTRRFSD | LGFEVKCFND | LKAEELLLKI | ||||
HEVSTVSHAD | ADCFVCVFLS | HGEGNHIYAY | DAKIEIQTLT | GLFKGDKCHS | ||||
LVGKPKIFII | QACRGNQHDV | PVIPLDVVDN | QTEKLDTNIT | EVDAASVYTL | ||||
PAGADFLMCY | SVAEGYYSHR | ETVNGSWYIQ | DLCEMLGKYG | SSLEFTELLT | ||||
LVNRKVSQRR | VDFCKDPSAI | GKKQVPCFAS | MLTKKLHFFP | KSN |
Funkcija
[uredi | uredi izvor]Ovaj gen kodira protein koji je član porodice cistein-aspartatnih proteaza (kaspaza). Sekvencna aktivacija kaspaza ima centralnu ulogu u fazi izvršenja ćelijskih apoptoza.[8] Kaspaze postoje kao neaktivni proenzimi koji se podvrgavaju proteolitskoj obrada na konzerviranim asparaginskim ostacima kako bi se dobile dvije podjedinice, velika i mala, koje se dimer pretvaraju u aktivni enzim. Ovaj protein se obrađuje kaspazama 7, 8 i 10, i smatra se da funkcioniše kao nizvodni enzim u kaskadi aktivacije kaspaze. Kaspaza-6 se također može podvrgnuti samoobradi bez drugih članova porodice kaspaza.[12] Alternativna prerada RNK ovog gena rezultira dvije varijante transkripta koje kodiraju različite izoforme.[13]
Kaspaza-6 ima ulogu u ranom imunskom odgovoru putem derepresije. Smanjuje ekspresiju imunosupresivnog citokina interleukina-10[9] i cijepa makrofage potiskujući IRAK-M.[10]
Što se tiče neurodegeneracija, kaspaza-6 cijepa HTT u Huntingtonovoj i APP u Alzheimerovoj bolesti. U oba slučaja rezultira agregacijom proteinskih fragmenata.[11]
Interakcije
[uredi | uredi izvor]Pokazalo se da kaspaza 6 reaguje sa kaspazom-8.[14][15][16]
Također pogledajte
[uredi | uredi izvor]Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000138794 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027997 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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.
- ^ 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.
- ^ "OrthoMaM phylogenetic marker: CASP6 coding sequence". Arhivirano s originala, 3. 3. 2016. Pristupljeno 20. 12. 2009.
- ^ a b Cohen, Gerald M. (15. 8. 1997). "Caspases: the executioners of apoptosis". Biochemical Journal (jezik: engleski). 326 (1): 1–16. doi:10.1042/bj3260001. ISSN 0264-6021. PMC 1218630. PMID 9337844.
- ^ a b c Bartel, Alexander; Göhler, André; Hopf, Verena; Breitbach, Katrin (7. 7. 2017). "Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines". PLOS ONE. 12 (7): e0180203. Bibcode:2017PLoSO..1280203B. doi:10.1371/journal.pone.0180203. ISSN 1932-6203. PMC 5501493. PMID 28686630.
- ^ a b Kobayashi, Hiroshi; Nolan, Anna; Naveed, Bushra; Hoshino, Yoshihiko; Segal, Leopoldo N.; Fujita, Yoko; Rom, William N.; Weiden, Michael D. (1. 1. 2011). "Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M". The Journal of Immunology (jezik: engleski). 186 (1): 403–410. doi:10.4049/jimmunol.1001906. ISSN 0022-1767. PMC 3151149. PMID 21098228.
- ^ a b Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. (1. 12. 2011). "Caspase-6 and neurodegeneration". Trends in Neurosciences (jezik: engleski). 34 (12): 646–656. doi:10.1016/j.tins.2011.09.001. ISSN 0166-2236. PMID 22018804. S2CID 1603684.
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- ^ "Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase".
- ^ 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.
- ^ 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.
- ^ 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. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.
Dopunska literatura
[uredi | uredi izvor]- Fernandes-Alnemri T, Litwack G, Alnemri ES (1995). "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. doi:10.1016/S0021-9258(18)47344-9. PMID 7983002.
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- Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES (1997). "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. Bibcode:1996PNAS...9314486S. doi:10.1073/pnas.93.25.14486. PMC 26159. PMID 8962078.
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- Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE (1998). "Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease". Science. 277 (5324): 373–6. CiteSeerX 10.1.1.1025.8052. doi:10.1126/science.277.5324.373. PMID 9219695.
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- Walter J, Schindzielorz A, Grünberg J, Haass C (1999). "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. Bibcode:1999PNAS...96.1391W. doi:10.1073/pnas.96.4.1391. PMC 15473. PMID 9990034.
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Vanjski linkovi
[uredi | uredi izvor]- The MEROPS online database for peptidases and their inhibitors: C14.005 Arhivirano 5. 2. 2008. na Wayback Machine
- P55212