An alternatively spliced C. elegans ced-4 RNA encodes a novel cell death inhibitor.
The C. elegans gene ced-4 is essential for programmed cell death. We report that ced-4 encodes two transcripts and that whereas the major transcript can cause programmed cell death, the minor transcript can act oppositely and prevent programmed cell death, thus defining a novel class of cell death inhibitors. That ced-4 has both cell-killing and cell-protective functions is consistent with previous genetic studies. Our results suggest that the dual protective and killer functions of the C. elegans bcl-2-like gene ced-9 are mediated by inhibition of the killer and protective ced-4 functions, respectively. We propose that a balance between opposing ced-4 functions influences the decision of a cell to live or to die by programmed cell death and that both ced-9 and ced-4 protective functions are required to prevent programmed cell death.
Shaham
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Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Horvitz
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HR
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics*; D017124:Conserved Sequence; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D017238:Genes, Helminth / Q000502:physiology; D015801:Helminth Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D012326:RNA Splicing / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; C089224:Ced-4 protein, C elegans; D015801:Helminth Proteins; D012333:RNA, Messenger