Shaham S
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-0448, USA.
J Biol Chem. 1998 Dec 25;273(52):35109-17. doi: 10.1074/jbc.273.52.35109.
Proteases of the caspase family play a central role in the execution of programmed cell death in all metazoans examined. The Caenorhabditis elegans caspase CED-3 is essential for programmed cell death in this organism. Three additional C. elegans caspase-related genes, csp-1 (caspase homolog-1), which encodes the csp-1A, csp-1B, and csp-1C RNA species; csp-2, which encodes the csp-2A and csp-2B RNA species; and csp-3 are identified. CSP-1A, CSP-1B, CSP-2A, and CSP-2B proteins are similar in sequence to caspase proproteins. CSP-1C is similar only to large caspase subunits, and CSP-3 is similar only to small caspase subunits. CSP-1B can be activated to become a cysteine protease by processing at internal aspartate residues. Activated CSP-1B can cleave the CSP-1B, CED-3, and CSP-2B proproteins, and activated CED-3 can cleave the CED-3 and CSP-2B proproteins. Inhibitor and synthetic substrate studies further suggest that activated CSP-1B and activated CED-3 have different substrate specificities. These results suggest that C. elegans encodes several caspases that might act in proteolytic cascades to regulate processes such as programmed cell death.
在所有已研究的后生动物中，半胱天冬酶家族的蛋白酶在程序性细胞死亡的执行过程中发挥着核心作用。秀丽隐杆线虫的半胱天冬酶CED-3对该生物体的程序性细胞死亡至关重要。另外还鉴定出三个与秀丽隐杆线虫半胱天冬酶相关的基因，即csp-1（半胱天冬酶同源物-1），它编码csp-1A、csp-1B和csp-1C RNA种类；csp-2，它编码csp-2A和csp-2B RNA种类；以及csp-3。CSP-1A、CSP-1B、CSP-2A和CSP-2B蛋白在序列上与半胱天冬酶原蛋白相似。CSP-1C仅与大的半胱天冬酶亚基相似，而CSP-3仅与小的半胱天冬酶亚基相似。CSP-1B可通过在内部分天冬氨酸残基处进行加工而被激活成为一种半胱氨酸蛋白酶。活化的CSP-1B可切割CSP-1B、CED-3和CSP-2B原蛋白，而活化的CED-3可切割CED-3和CSP-2B原蛋白。抑制剂和合成底物研究进一步表明，活化的CSP-1B和活化的CED-3具有不同的底物特异性。这些结果表明，秀丽隐杆线虫编码了几种半胱天冬酶，它们可能在蛋白水解级联反应中发挥作用，以调节程序性细胞死亡等过程。
