Prevention of apoptosis of mammalian cells by the CED-3-cleaved form of CED-9.
CED-9 prevents apoptosis in embryonic cells of Caenorhabditis elegans but not in mammalian cells. We show here that the prevention of apoptosis in mammalian cells requires a CED-3-cleaved form (68-280) of CED-9 which is localized in the inner mitochondrial membrane. The viability of PC12 and HeLa cells was significantly increased after death stimuli when truncated CED-9 was expressed in these cells but full-length CED-9 did not. The truncated CED-9 expressed in these cells was largely localized to the inner mitochondrial and the endoplasmic reticulum membranes, while full-length CED-9 was detected mainly in endoplasmic reticulum fractions. Moreover, truncated CED-9 in purified mitochondria was resistant to trypsin digestion, but full-length CED-9 was not. These results suggest that the CED-3-cleaved form of CED-9 prevents apoptosis in mammalian cells by localizing to the inner mitochondrial membrane.
Shibata
M
M
Department of Cell Biology and Neuroscience, Osaka University Graduate School of Medicine, Suita, Japan.
Kanamori
S
S
Ohsawa
Y
Y
Watanabe
T
T
Yayoi
Y
Y
Miura
M
M
Kominami
E
E
Uchiyama
Y
Y
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; D020169:Caspases / Q000502:physiology*; D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D006367:HeLa Cells; D015801:Helminth Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007425:Intracellular Membranes / Q000648:ultrastructure; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D009154:Mutation; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats
D051017:Apoptosis Regulatory Proteins; D029742:Caenorhabditis elegans Proteins; C087233:Ced-9 protein, C elegans; D015801:Helminth Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases; C089223:ced-3 protein, C elegans