The Caenorhabditis 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 family.
ced-9 and
bcl-2 were discovered because of the effects of dominant gain-of-function mutations. 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 cells. Here we report that, by contrast, the
ced-9(
n1950) gain-of-function mutation affects the open reading frame of
ced-9 and 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 alteration of this glycine in other members of the
ced-9/bcl-2 family might lead to oncogenic activation. We also present genetic evidence suggesting that the CED-9 protein might exist in two distinct forms that have opposite effects on cell death.AD - Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.FAU - Hengartner, M OAU - Hengartner MOFAU - Horvitz, H RAU - Horvitz HRLA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Ced-9 protein)RN - 0 (Glutamates)RN - 0 (Helminth Proteins)RN - 0 (Proto-Oncogene Proteins)RN - 0 (Proto-Oncogene Proteins c-
bcl-2)RN - 56-40-6 (Glycine)RN - 56-86-0 (Glutamic Acid)SB - IM