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.
- ^ 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.
- ^ "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.
- Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC (1996). "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. Bibcode:1996PNAS...93.8395T. doi:10.1073/pnas.93.16.8395. PMC 38682. PMID 8710882.
- Bullrich F, Fernandes-Alnemri T, Litwack G, Alnemri ES, Croce CM (1997). "Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3". Genomics. 36 (2): 362–5. doi:10.1006/geno.1996.0476. PMID 8812467.
- Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES (1996). "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. doi:10.1074/jbc.271.43.27099. PMID 8900201.
- 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.
- Rao L, Perez D, White E (1997). "Lamin proteolysis facilitates nuclear events during apoptosis". J. Cell Biol. 135 (6 Pt 1): 1441–55. doi:10.1083/jcb.135.6.1441. PMC 2133948. PMID 8978814.
- 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.
- 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 (1997). "FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542–5. doi:10.1074/jbc.272.30.18542. PMID 9228018.
- Caulín C, Salvesen GS, Oshima RG (1997). "Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis". J. Cell Biol. 138 (6): 1379–94. doi:10.1083/jcb.138.6.1379. PMC 2132555. PMID 9298992.
- Hirata H, Takahashi A, Kobayashi S, Yonehara S, Sawai H, Okazaki T, Yamamoto K, Sasada M (1998). "Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis". J. Exp. Med. 187 (4): 587–600. doi:10.1084/jem.187.4.587. PMC 2212161. PMID 9463409.
- Harvey KF, Harvey NL, Michael JM, Parasivam G, Waterhouse N, Alnemri ES, Watters D, Kumar S (1998). "Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis". J. Biol. Chem. 273 (22): 13524–30. doi:10.1074/jbc.273.22.13524. PMID 9593687.
- Utz PJ, Hottelet M, Le TM, Kim SJ, Geiger ME, van Venrooij WJ, Anderson P (1999). "The 72-kDa component of signal recognition particle is cleaved during apoptosis". J. Biol. Chem. 273 (52): 35362–70. doi:10.1074/jbc.273.52.35362. PMID 9857079.
- Samejima K, Svingen PA, Basi GS, Kottke T, Mesner PW, Stewart L, Durrieu F, Poirier GG, Alnemri ES, Champoux JJ, Kaufmann SH, Earnshaw WC (1999). "Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis". J. Biol. Chem. 274 (7): 4335–40. doi:10.1074/jbc.274.7.4335. PMID 9933635.
- 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.
- 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 (1999). "Identification of caspases that cleave presenilin-1 and presenilin-2. Five presenilin-1 (PS1) mutations do not alter the sensitivity of PS1 to caspases" (PDF). FEBS Lett. 445 (1): 149–54. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/238040151162165141. PMID 10069390. S2CID 31218178.
- Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson DW (1999). "Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis". EMBO J. 18 (8): 2049–56. doi:10.1093/emboj/18.8.2049. PMC 1171289. PMID 10205159.
Vanjski linkovi[uredi | uredi izvor]
- The MEROPS online database for peptidases and their inhibitors: C14.005 Arhivirano 5. 2. 2008. na Wayback Machine
- P55212
