Regulation of apoptosis by a Caenorhabditis elegans BNIP3 homolog.
We have identified a C. elegans protein, ceBNIP3, homologous to the human BCL-2/EIB-19K interacting BCL-2 family pro-apoptotic protein BNIP3. In transiently transfected mammalian cells, ceBNIP3 complexes with CED-9, the worm homolog of BCL-2. CeBNIP3 also efficiently heterodimerizes with the cell death protease proCED-3 by direct binding via the prodomain. Transfection of ceBNIP3 and CED-3 results in enhanced proteolytic processing of the CED-3 zymogen and in cooperative induction of apoptosis. Coexpression of CED-9 suppresses the cooperative cell death induced by ceBNIP3 and CED-3. In cells coexpressing CED-9, ceBNIP3 and CED-3, all three proteins exist as a ternary complex suggesting that CED-9 may suppress cooperative apoptosis induced by CED-3 and ceBNIP3 by simultaneous complex formation with CED-3 and ceBNIP3. Our results suggest that ceBNIP3 may be a novel component of the C. elegans apoptosis paradigm and may initiate apoptosis by recruiting CED-3 to mitochondria and other cytoplasmic membranes.
Yasuda
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M
Institute for Molecular Virology, St Louis University Medical Center, Missouri 63110, USA.
D'Sa-Eipper
C
C
Gong
X L
XL
Chinnadurai
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G
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014162:Transfection; D025521:Tumor Suppressor Proteins
D051017:Apoptosis Regulatory Proteins; C090121:BNIP3 protein, human; C116838:BNIP3L protein, human; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C087233:Ced-9 protein, C elegans; C115798:DCT-1 protein, C elegans; D015801:Helminth Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans