Abstract
THE Caenofhabditis elegans gene ced-9 and the human proto-oncogene bcl-2, both of which protect cells from programmed cell death, are members of the same gene family1–11, ced-9 and bcl-2 were discovered because of the effects of dominant gain-of-function mutations12–14. Such bcl-2 mutations, which are commonly found in follicular lymphoma, are translocations that result in over-expression of a normal Bcl-2 protein in B cells1,13–16. Here we report that, by contrast, the ced-9(n1950) gain-of-function muta-tion affects the open reading frame of ced-9and results in a glycine-to-glutamate substitution in a region highly conserved among all ced-9/ bcl-2 family members. We conclude that this glycine has an important function in ced-9 regulation, and we suggest that altera-tion of this glycine in other members of the ced-9/bcl-2 family might lead to oncogenic activation. We also present genetic evi-dence suggesting that the CED-9 protein might exist in two distinct forms that have opposite effects on cell death.
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Hengartner, M., Horvitz, H. Activation of C. elegans cell death protein CED-9 by an ammo-acid substitution in a domain conserved in Bcl-2. Nature 369, 318–320 (1994). https://doi.org/10.1038/369318a0
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DOI: https://doi.org/10.1038/369318a0