胱天蛋白酶6
外观
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胱天蛋白酶6(英语:Caspase 6)是人类中由CASP6基因编码的一种酶。[5][6]许多可获得完整基因组数据的哺乳动物中都已鉴定出CASP6直向同源物。[7]鸟类、蜥蜴、滑体动物和真骨类中也存在独特的直系同源物。胱天蛋白酶6在亨廷顿舞蹈症和阿尔茨海默病的细胞凋亡、[8]早期免疫反应[9][10]和神经变性中具有重要功能。[11]
作用
[编辑]该基因编码的蛋白质是胱天蛋白酶家族的成员。胱天蛋白酶的连续激活在细胞凋亡的执行阶段发挥着核心作用。[8]胱天蛋白酶以无活性的酶原形式存在,在保守的天冬氨酸残基处经历蛋白水解加工,产生一大一小两个亚基,然后二聚化形成活性酶。该蛋白由胱天蛋白酶7、8和10加工,被认为是胱天蛋白酶激活级联中的下游酶。胱天蛋白酶6也可以在没有胱天蛋白酶家族其他成员的情况下进行自我加工。[12]该基因的选择性剪接产生了编码不同亚型的两个转录变体。[13]
胱天蛋白酶6通过去抑制在早期免疫反应中发挥作用。它降低免疫抑制剂细胞因子白细胞介素10[9]的表达,并裂解巨噬细胞上表达的IRAK-M来抑制巨噬细胞。[10]
对于神经变性,胱天蛋白酶6可以裂解亨廷顿舞蹈症中的亨廷顿蛋白(HTT)和阿尔茨海默病中的前类淀粉蛋白质(APP)。这两种情况都会导致片段的蛋白质聚集。[11]
相互作用
[编辑]胱天蛋白酶6已被证明与胱天蛋白酶8发生相互作用。[14][15][16]
参见
[编辑]参考文献
[编辑]- ^ 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.
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- ^ OrthoMaM phylogenetic marker: CASP6 coding sequence. [2009-12-20]. (原始内容存档于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
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- ^ 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
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- ^ 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
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- ^ 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
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- ^ Entrez Gene: CASP6 caspase 6, apoptosis-related cysteine peptidase.
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- ^ 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
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- ^ 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
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拓展阅读
[编辑]- 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
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- 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
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.
- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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. (原始内容存档 (PDF)于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
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外部链接
[编辑]- 肽酶及其抑制剂的MEROPS在线数据库:C14.005 (页面存档备份,存于互联网档案馆)
- PDB中UniProt可用的所有結構信息之概述:P55212 (Human Caspase-6) 在PDBe-KB。
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