The Caenorhabditis elegans sex determination protein FEM-1 is a CED-3 substrate that associates with CED-4 and mediates apoptosis in mammalian cells.
Sex-specific elimination of cells by apoptosis plays a role in sex determination in Caenorhabditis elegans. Recently, a mammalian pro-apoptotic protein named F1Aalpha has been identified. F1Aalpha shares extensive homology throughout the entire protein with the C. elegans protein, FEM-1, which is essential for achieving all aspects of the male phenotype in the nematode. In this report, the role of FEM-1 in apoptosis was investigated. Overexpression of FEM-1 induces caspase-dependent apoptosis in mammalian cells. FEM-1 is cleaved in vitro by the C. elegans caspase, CED-3, generating an N-terminal cleavage product that corresponds to the minimal effector domain for apoptosis. Furthermore, CED-4 associates with FEM-1 in vitro and in vivo in mammalian cells and potentiates FEM-1-mediated apoptosis. Similarly, Apaf-1, the mammalian homologue of CED-4 was found to associate with F1Aalpha. These data suggest that FEM-1 and F1Aalpha may mediate apoptosis by communicating directly with the core machinery of apoptosis.
Chan
S L
SL
Institute of Molecular and Cell Biology, 30 Medical Dr., Singapore 117609, Republic of Singapore.
Yee
K S
KS
Tan
K M
KM
Yu
V C
VC
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D020169:Caspases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; D018797:Cell Cycle Proteins; C115306:FEM-1 protein, C elegans; D015801:Helminth Proteins; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans