胱天蛋白酶6
胱天蛋白酶6（英語：Caspase 6）是人類中由CASP6基因編碼的一種酶。[5][6]許多可獲得完整基因組資料的哺乳動物中都已鑑定出CASP6直向同源物。[7]鳥類、蜥蜴、滑體動物和真骨類中也存在獨特的直系同源物。胱天蛋白酶6在亨廷頓舞蹈症和阿茲海默症的細胞凋亡、[8]早期免疫反應[9][10]和神經變性中具有重要功能。[11]
作用
該基因編碼的蛋白質是胱天蛋白酶家族的成員。胱天蛋白酶的連續活化在細胞凋亡的執行階段發揮著核心作用。[8]胱天蛋白酶以無活性的酶原形式存在，在保守的天門冬胺酸殘基處經歷蛋白水解加工，產生一大一小兩個亞基，然後二聚化形成活性酶。該蛋白由胱天蛋白酶7、8和10加工，被認為是胱天蛋白酶活化級聯中的下游酶。胱天蛋白酶6也可以在沒有胱天蛋白酶家族其他成員的情況下進行自我加工。[12]該基因的選擇性剪接產生了編碼不同亞型的兩個轉錄變體。[13]
胱天蛋白酶6通過去抑制在早期免疫反應中發揮作用。它降低免疫抑制劑細胞因子白血球介素10[9]的表現，並裂解巨噬細胞上表現的IRAK-M來抑制巨噬細胞。[10]
對於神經變性，胱天蛋白酶6可以裂解亨廷頓舞蹈症中的亨廷頓蛋白（HTT）和阿茲海默症中的前類澱粉蛋白質（APP）。這兩種情況都會導致片段的蛋白質聚集。[11]
相互作用
胱天蛋白酶6已被證明與胱天蛋白酶8發生相互作用。[14][15][16]
參見
參考文獻
- ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000138794 - Ensembl, May 2017
- ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000027997 - Ensembl, May 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. Chromosomal localization of the human genes, CPP32, Mch2, Mch3, and Ich-1, involved in cellular apoptosis. Biochem Biophys Res Commun. Oct 1996, 225 (3): 983–9. PMID 8780721. doi:10.1006/bbrc.1996.1282.
- ^ Fernandes-Alnemri T, Litwack G, Alnemri ES. Mch2, a new member of the apoptotic Ced-3/Ice cysteine protease gene family. Cancer Res. Aug 1995, 55 (13): 2737–42. PMID 7796396.
- ^ OrthoMaM phylogenetic marker: CASP6 coding sequence. [2009-12-20]. （原始內容存檔於2016-03-03）.
- ^ 8.0 8.1 Cohen, Gerald M. Caspases: the executioners of apoptosis. Biochemical Journal. 1997-08-15, 326 (1): 1–16. ISSN 0264-6021. PMC 1218630
. PMID 9337844. doi:10.1042/bj3260001 （英語）.
- ^ 9.0 9.1 Bartel, Alexander; Göhler, André; Hopf, Verena; Breitbach, Katrin. Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines. PLOS ONE. 2017-07-07, 12 (7): e0180203. Bibcode:2017PLoSO..1280203B. ISSN 1932-6203. PMC 5501493 . PMID 28686630. doi:10.1371/journal.pone.0180203 .
- ^ 10.0 10.1 Kobayashi, Hiroshi; Nolan, Anna; Naveed, Bushra; Hoshino, Yoshihiko; Segal, Leopoldo N.; Fujita, Yoko; Rom, William N.; Weiden, Michael D. Neutrophils Activate Alveolar Macrophages by Producing Caspase-6–Mediated Cleavage of IL-1 Receptor-Associated Kinase-M. The Journal of Immunology. 2011-01-01, 186 (1): 403–410. ISSN 0022-1767. PMC 3151149 . PMID 21098228. doi:10.4049/jimmunol.1001906 （英語）.
- ^ 11.0 11.1 Graham, Rona K.; Ehrnhoefer, Dagmar E.; Hayden, Michael R. Caspase-6 and neurodegeneration. Trends in Neurosciences. 2011-12-01, 34 (12): 646–656 [2024-02-02]. ISSN 0166-2236. PMID 22018804. S2CID 1603684. doi:10.1016/j.tins.2011.09.001. （原始內容存檔於2013-10-16） （英語）.
- ^ Wang XJ, Cao Q, Liu X, Wang KT, Mi W, Zhang Y, Li LF, LeBlanc AC, Su XD. Crystal structures of human caspase 6 reveal a new mechanism for intramolecular cleavage self-activation. EMBO Rep. Nov 2010, 11 (11): 841–7. PMC 2966951 . PMID 20890311. doi:10.1038/embor.2010.141.
- ^ Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase.
- ^ Cowling V, Downward J. 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. Oct 2002, 9 (10): 1046–56. PMID 12232792. doi:10.1038/sj.cdd.4401065 .
- ^ Guo Y, Srinivasula SM, Druilhe A, Fernandes-Alnemri T, Alnemri ES. Caspase-2 induces apoptosis by releasing proapoptotic proteins from mitochondria. J. Biol. Chem. Apr 2002, 277 (16): 13430–7. PMID 11832478. doi:10.1074/jbc.M108029200 .
- ^ Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES. 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. Dec 1996, 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. PMC 26159 . PMID 8962078. doi:10.1073/pnas.93.25.14486 .
拓展閱讀
- Fernandes-Alnemri T, Litwack G, Alnemri ES. 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. 1995, 269 (49): 30761–4. PMID 7983002. doi:10.1016/S0021-9258(18)47344-9 .
- Takahashi A, Alnemri ES, Lazebnik YA, Fernandes-Alnemri T, Litwack G, Moir RD, Goldman RD, Poirier GG, Kaufmann SH, Earnshaw WC. 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. 1996, 93 (16): 8395–400. Bibcode:1996PNAS...93.8395T. PMC 38682 . PMID 8710882. doi:10.1073/pnas.93.16.8395 .
- Bullrich F, Fernandes-Alnemri T, Litwack G, Alnemri ES, Croce CM. Chromosomal mapping of cell death proteases CPP32, MCH2, and MCH3. Genomics. 1997, 36 (2): 362–5. PMID 8812467. doi:10.1006/geno.1996.0476.
- Srinivasula SM, Fernandes-Alnemri T, Zangrilli J, Robertson N, Armstrong RC, Wang L, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES. 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. 1996, 271 (43): 27099–106. PMID 8900201. doi:10.1074/jbc.271.43.27099 .
- Srinivasula SM, Ahmad M, Fernandes-Alnemri T, Litwack G, Alnemri ES. 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. 1997, 93 (25): 14486–91. Bibcode:1996PNAS...9314486S. PMC 26159 . PMID 8962078. doi:10.1073/pnas.93.25.14486 .
- Rao L, Perez D, White E. Lamin proteolysis facilitates nuclear events during apoptosis. J. Cell Biol. 1997, 135 (6 Pt 1): 1441–55. PMC 2133948 . PMID 8978814. doi:10.1083/jcb.135.6.1441.
- Kim TW, Pettingell WH, Jung YK, Kovacs DM, Tanzi RE. Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science. 1998, 277 (5324): 373–6. CiteSeerX 10.1.1.1025.8052 . PMID 9219695. doi:10.1126/science.277.5324.373.
- 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. FLAME-1, a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis. J. Biol. Chem. 1997, 272 (30): 18542–5. PMID 9228018. doi:10.1074/jbc.272.30.18542 .
- Caulín C, Salvesen GS, Oshima RG. Caspase Cleavage of Keratin 18 and Reorganization of Intermediate Filaments during Epithelial Cell Apoptosis. J. Cell Biol. 1997, 138 (6): 1379–94. PMC 2132555 . PMID 9298992. doi:10.1083/jcb.138.6.1379.
- Hirata H, Takahashi A, Kobayashi S, Yonehara S, Sawai H, Okazaki T, Yamamoto K, Sasada M. Caspases Are Activated in a Branched Protease Cascade and Control Distinct Downstream Processes in Fas-induced Apoptosis. J. Exp. Med. 1998, 187 (4): 587–600. PMC 2212161 . PMID 9463409. doi:10.1084/jem.187.4.587.
- Harvey KF, Harvey NL, Michael JM, Parasivam G, Waterhouse N, Alnemri ES, Watters D, Kumar S. Caspase-mediated cleavage of the ubiquitin-protein ligase Nedd4 during apoptosis. J. Biol. Chem. 1998, 273 (22): 13524–30. PMID 9593687. doi:10.1074/jbc.273.22.13524 .
- Utz PJ, Hottelet M, Le TM, Kim SJ, Geiger ME, van Venrooij WJ, Anderson P. The 72-kDa component of signal recognition particle is cleaved during apoptosis. J. Biol. Chem. 1999, 273 (52): 35362–70. PMID 9857079. doi:10.1074/jbc.273.52.35362 .
- Samejima K, Svingen PA, Basi GS, Kottke T, Mesner PW, Stewart L, Durrieu F, Poirier GG, Alnemri ES, Champoux JJ, Kaufmann SH, Earnshaw WC. Caspase-mediated cleavage of DNA topoisomerase I at unconventional sites during apoptosis. J. Biol. Chem. 1999, 274 (7): 4335–40. PMID 9933635. doi:10.1074/jbc.274.7.4335 .
- Walter J, Schindzielorz A, Grünberg J, Haass C. Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis. Proc. Natl. Acad. Sci. U.S.A. 1999, 96 (4): 1391–6. Bibcode:1999PNAS...96.1391W. PMC 15473 . PMID 9990034. doi:10.1073/pnas.96.4.1391 .
- 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. 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. 1999, 445 (1): 149–54 [2024-02-02]. PMID 10069390. S2CID 31218178. doi:10.1016/S0014-5793(99)00108-8. hdl:10067/238040151162165141 . （原始內容存檔 (PDF)於2023-12-02）.
- Xanthoudakis S, Roy S, Rasper D, Hennessey T, Aubin Y, Cassady R, Tawa P, Ruel R, Rosen A, Nicholson DW. Hsp60 accelerates the maturation of pro-caspase-3 by upstream activator proteases during apoptosis. EMBO J. 1999, 18 (8): 2049–56. PMC 1171289 . PMID 10205159. doi:10.1093/emboj/18.8.2049.
