Evidence against a functional site for Bcl-2 downstream of caspase cascade in preventing apoptosis.
Apoptotic cell death is driven by ICE family proteases (caspases) and negatively regulated by Bcl-2 family proteins. Although it has been shown that Bcl-2 exerts anti-apoptotic activity by blocking a step(s) leading to the activation of caspases, a role for Bcl-2 and Bcl-xL downstream of the caspase cascade has remained unclear. Here, we show that purified active caspase-3 (CPP32/Yama/apopain) and caspase-1 (ICE) induces apoptosis when microinjected into the cytoplasm of cells, confirming our recent observations, and that the apoptosis is not at all prevented by Bcl-2 and Bcl-xL, which are overexpressed more than sufficiently to prevent Fas-mediated and overexpressed procaspase-1-mediated apoptosis. Thus, Bcl-2 and Bcl-xL do not act downstream of the caspase cascade.
Yasuhara
N
N
Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Sahara
S
S
Kamada
S
S
Eguchi
Y
Y
Tsujimoto
Y
Y
D017209:Apoptosis; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008845:Microinjections; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D004792:Enzyme Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D003546:Cysteine Endopeptidases