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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Cleary, M. L., Smith, S. D. & Sklar, J. Cell 47, 19–28 (1986).
Pearson, G. R. et al. Virology 160, 151–161 (1987).
Oltvari, Z. N., Milliman, C. L. & Korsmeyer, S. J. Cell 74, 609–619 (1993).
Boise, L. H. et al. Cell 74, 597–608 (1993).
Kozopas, K. M., Yang, T., Buchan, H. L., Zhou, P. & Craig, R. W. Proc. natn. Acad. Sci. U.S.A. 90, 3516–3520 (1993).
Lin, E. Y., Orlofsky, A., Berger, M. S. & Prystowsky, M. B. J. Immun. 151, 1979–1988 (1993).
Hengartner, M. O. & Horvitz, H. R. Cell 76, 665–676 (1994).
Neilan, J. G. et al. J. Virol. 67, 4391–4394 (1993).
Albrecht, J.-C. et al. J. Virol. 66, 5047–5058 (1992).
Williams, G. T. & Smith, C. A. Cell 74, 777–779 (1993).
Hergartner, M. O. & Horvitz, H. R. Curr. Opin. Genet. Dev. (in the press).
Hengartner, M. O., Ellis, R. E. & Horvitz, H. R. Nature 356, 494–499 (1992).
Yunis, J. J. et al. New Engl. J. Med. 307, 1231–1236 (1982).
Tsujimoto, Y., Finger, L. R., Yunis, J., Nowell, P. C. & Croce, C. M. Science 226, 1097–1099 (1984).
Tsujimoto, Y. & Croce, C. M. Proc. natn. Acad. Sci. U.S.A. 83, 5214–5218 (1986).
Seto, M. et al. EMBO J. 7, 123–131 (1988).
Vaux, D. L., Weissman, I. L. & Kim, S. K. Science 258, 1955–1957 (1992).
Yuan, J. & Horvitz, H. R. Development 116, 309–320 (1992).
Yin, X.-M., Oltvai, Z. N. & Korsmeyer, S. J. Nature 369, 321–323 (1994).
Korsmeyer, S. J., Shutter, J. R., Veis, D. J., Merry, D. E. & Oltvai, Z. N. Semin. Cancer Biol. 4, 327–333 (1993).
Ellis, H. M. & Horvitz, H. R. Cell 44, 817–829 (1986).
Cazals-Hatem, D. L., Louie, D. C., Tanaka, S. & Reed, J. C. Biochim. biophys. Acta 1143, 109–113 (1992).
Eguchi, Y., Ewert, D. L. & Tsujimoto, Y. Nucleic Acids Res. 20, 4187–4192 (1992).
Avery, L. & Horvitz, H. R. Cell 51, 1071–1078 (1987).
Sulston, J. E. & Horvitz, H. R. Devl Biol. 56, 110–156 (1977).
Negrini, M., Silini, E., Kozak, C., Tsujimoto, Y. & Croce, C. M. Cell 49, 455–463 (1987).
Files, J. G., Carr, S. & Hirsh, D. J. molec. Biol. 164, 355–375 (1983).
Mello, C. C., Kramer, J. M., Stinchcomb, D. T. & Ambros, V. EMBO J. 10, 3959–3970 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/369318a0
This article is cited by
-
Downregulated RPS-30 in Angiostrongylus cantonensis L5 plays a defensive role against damage due to oxidative stress
Parasites & Vectors (2020)
-
Noncanonical cell death programs in the nematode Caenorhabditis elegans
Cell Death & Differentiation (2008)
-
egl-1: a key activator of apoptotic cell death in C. elegans
Oncogene (2008)
-
The BCL-2 protein family: opposing activities that mediate cell death
Nature Reviews Molecular Cell Biology (2008)
-
Regulation of apoptosis by C. elegans CED-9 in the absence of the C-terminal transmembrane domain
Cell Death & Differentiation (2007)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
