Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Meeting Report
  • Published:

Life and death in paradise

Abstract

Over 500 researchers participated in a recent American Association for Cancer Research special conference, entitled “Apoptosis and Cancer: Basic Mechanisms and Therapeutic Opportunities in the Post-Genomic Era” (February 13–17, 2002) in sunny Hawaii (Hilton Waikoloa village, Kona, Hawaii). The meeting participants presented the most recent findings on the mechanisms regulating cell death in cancer. In the past decade, apoptosis research has undergone a quantum leap, metamorphosing from a descriptive, phenomenological discipline into a molecularly defined, highly complex signalling field. This transformation was highlighted in the conference's opening talk by meeting co-organizer, John Reed (The Burnham Institute, La Jolla, CA). Reed and colleagues used published protein functional information and bio-informatic mining of the available human genome databases to tabulate the number of human proteins predicted to be involved in regulating apoptosis. The list includes 11 catalytically active caspases, 26 CARD (caspase associated recruitment domain)-, 32 DD (death domain)-, 12 DED (death effector domain)-, 8 BIR (baculovirus inhibitor of apoptosis protein region)-, 24 BH (Bcl-2 homology)-, and 34 PAAD/PYD (pyrin/PAAD)-containing sequences.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: A schematic representation demonstrating the role of apoptosis in the prevention of cancer.

References

  1. Metzstein, M. M., Stanfield, G. M. & Horvitz, H. R. Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet. 14, 410–416 (1998).

    Article  CAS  Google Scholar 

  2. Gartner, A., Milstein, S., Ahmed, S., Hodgkin, J. & Hengartner, M. O. A conserved checkpoint pathway mediates DNA damage-induced apoptosis and cell cycle arrest in C. elegans. Mol. Cell 5, 435–443 (2000).

    Article  CAS  Google Scholar 

  3. Wu, G. et al. Structural basis of IAP recognition by Smac/DIABLO. Nature 408, 1008–1012 (2000).

    Article  CAS  Google Scholar 

  4. Liu, Z. et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature 408, 1004–1008 (2000).

    Article  CAS  Google Scholar 

  5. Srinivasula, S. M. et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410, 112–116 (2001).

    Article  CAS  Google Scholar 

  6. Christich, A. et al. The damage-responsive Drosophila gene sickle encodes a novel IAP binding protein similar to but distinct from reaper, grim, and hid. Curr. Biol. 12, 137–140 (2002).

    Article  CAS  Google Scholar 

  7. Srinivasula, S. M. et al. Sickle, a novel Drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein. Curr. Biol. 12, 125–130 (2002).

    Article  CAS  Google Scholar 

  8. Suzuki, Y. et al. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol. Cell 8, 613–621 (2001).

    Article  CAS  Google Scholar 

  9. Inukai, T. et al. SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. Mol. Cell 4, 343–352 (1999).

    Article  CAS  Google Scholar 

  10. Conradt, B. & Horvitz, H. R. The TRA-1A sex determination protein of C. elegans regulates sexually dimorphic cell deaths by repressing the egl-1 cell death activator gene. Cell 98, 317–327 (1999).

    Article  CAS  Google Scholar 

  11. Paroni, G., Henderson, C., Schneider, C. & Brancolini, C. Caspase-2 can trigger cytochrome c release and apoptosis from the nucleus. J. Biol. Chem. 277, 15147–15161 (2002).

    Article  CAS  Google Scholar 

  12. Pelengaris, S., Khan, M. & Evan, G. I. Suppression of Myc-induced apoptosis in β cells exposes multiple oncogenic properties of Myc and triggers carcinogenic progression. Cell 109, 321–334 (2002).

    Article  CAS  Google Scholar 

  13. Briasoulis, E. et al. Near-absolute expression of the bcl-2 protein identifies a subgroup of stage II breast cancer patients with a most favorable outcome. Results of a clinicopathological study. J. Exp. Clin. Cancer Res. 20, 341–344 (2001).

    CAS  Google Scholar 

  14. Schmitt, C. A. & Lowe, S. W. Bcl-2 mediates chemoresistance in matched pairs of primary E(μ)–Myc lymphomas in vivo. Blood Cells Mol. Dis. 27, 206–216 (2001).

    Article  CAS  Google Scholar 

  15. LeBlanc, H. et al. Tumor-cell resistance to death receptor—induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nature Med. 8, 274–281 (2002).

    Article  CAS  Google Scholar 

  16. Plas, D. R. & Thompson, C. B. Cell metabolism in the regulation of programmed cell death. Trends Endocrinol. Metabolism 13, 75–78 (2002).

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a grant from the National Cancer Institute (CA89434) to J.Y., a K08 Award (AG19245) to O.G. and a Postdoctoral Fellowship from the American Cancer Society to L.Y.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gozani, O., Boyce, M., Yoo, L. et al. Life and death in paradise. Nat Cell Biol 4, E159–E162 (2002). https://doi.org/10.1038/ncb0602-e159

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb0602-e159

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing