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
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
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).
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).
Wu, G. et al. Structural basis of IAP recognition by Smac/DIABLO. Nature 408, 1008–1012 (2000).
Liu, Z. et al. Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain. Nature 408, 1004–1008 (2000).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Plas, D. R. & Thompson, C. B. Cell metabolism in the regulation of programmed cell death. Trends Endocrinol. Metabolism 13, 75–78 (2002).
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
Rights 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
Issue Date:
DOI: https://doi.org/10.1038/ncb0602-e159
