title: Caenorhabditis elegans caspase homolog CSP-2 inhibits CED-3 autoactivation and apoptosis in germ cells.
abstract: In Caenorhabditis elegans, apoptosis in germ cells is mediated by the same core apoptotic machinery that controls apoptosis in somatic cells. These include the CED-3 caspase, the CED-3 activator CED-4, and the cell death inhibitor CED-9. However, germline apoptosis also differs from somatic apoptosis in its regulation. We found that CSP-3, a caspase homolog that blocks CED-3 autoactivation and apoptosis in somatic cells, does not affect apoptosis in germ cells. Interestingly, the second C. elegans caspase homolog, CSP-2, shares sequence similarity to both catalytic subunits of the CED-3 caspase, and surprisingly, contains a stretch of sequence that is almost identical to that of CSP-3. Unlike CSP-3 that acts specifically in somatic cells, loss of CSP-2 causes increased apoptosis only in germ cells, suggesting that CSP-2 is a germ cell-specific apoptosis inhibitor. Moreover, like CSP-3, CSP-2 associates with the CED-3 zymogen and inhibits its autoactivation, but does not inhibit CED-4-induced CED-3 activation or the activity of the activated CED-3 protease. Thus, two different C. elegans caspase homologs use the same mechanism to prevent caspase autoactivation and apoptosis in different tissues, suggesting that this could be a generally applicable strategy for regulating caspase activation and apoptosis.
authors: Department of Molecular, Cellular, and Developmental Biology, Campus Box 347, University of Colorado, Boulder, CO 80309, USA.
authors: X
authors: X
authors: Geng
authors: Q H
authors: QH
authors: Zhou
authors: E
authors: E
authors: Kage-Nakadai
authors: Y
authors: Y
authors: Shi
authors: N
authors: N
authors: Yan
authors: S
authors: S
authors: Mitani
authors: D
authors: D
authors: Xue
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D053143:Caspase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000737:chemistry / Q000378:metabolism*; D005854:Germ Cells / Q000166:cytology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; D053143:Caspase 2; D020169:Caspases; C089223:ced-3 protein, C elegans