RRC ID 4327
Author Geng X, Shi Y, Nakagawa A, Yoshina S, Mitani S, Shi Y, Xue D.
Title Inhibition of CED-3 zymogen activation and apoptosis in Caenorhabditis elegans by caspase homolog CSP-3.
Journal Nat. Struct. Mol. Biol.
Abstract Inhibitor of apoptosis (IAP) proteins have a crucial role in apoptosis, through negative regulation of caspases in species from fruitflies to mammals. In Caenorhabditis elegans, however, no IAP homolog or caspase inhibitor has been identified, calling into question how the cell-killing caspase CED-3 can be negatively regulated. Here we show that inactivation of the C. elegans csp-3 gene, which encodes a protein similar to the small subunit of the CED-3 caspase, causes cells that normally live to undergo apoptosis in a CED-3-dependent manner. Biochemical analysis reveals that CSP-3 associates with the large subunit of the CED-3 zymogen and inhibits zymogen autoactivation. However, CSP-3 does not block CED-3 activation induced by CED-4, nor does it inhibit the activity of the activated CED-3 protease. Therefore CSP-3 uses a previously unreported mechanism to protect cells from apoptosis.
Volume 15(10)
Pages 1094-101
Published 2008-10
DOI 10.1038/nsmb.1488
PII nsmb.1488
PMID 18776901
PMC PMC2574878
MeSH Amino Acid Sequence Animals Apoptosis* Caenorhabditis elegans / cytology* Caenorhabditis elegans / embryology Caenorhabditis elegans / enzymology* Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / antagonists & inhibitors* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Caspase Inhibitors* Caspases / chemistry Caspases / genetics Caspases / metabolism* Conserved Sequence Enzyme Activation Molecular Sequence Data Mutation / genetics Protein Subunits / chemistry Protein Subunits / genetics Protein Subunits / metabolism Sequence Alignment
IF 12.109
Times Cited 21
C.elegans tm2260 tm2486