Identification of multiple Caenorhabditis elegans caspases and their potential roles in proteolytic cascades.
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.
Shaham
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Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-0448, USA. shaham@cgl.ucsf.edu
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D053143:Caspase 2; D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D004926:Escherichia coli / Q000378:metabolism; D017238:Genes, Helminth; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D018510:RNA, Helminth / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013379:Substrate Specificity
D029742:Caenorhabditis elegans Proteins; D018510:RNA, Helminth; D012333:RNA, Messenger; D053143:Caspase 2; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans; C116781:csp-1 protein, C elegans; C116783:csp-3 protein, C elegans