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.

  • News & Views
  • Published:

Apoptosis

Placing death under control

Nature volume 388, pages 123–125 (1997)Cite this article

Unlike the gloomy connotation of the death of an organism, the death of an individual cell is an integral and continuing part of normal physiology1. It is also a major form of defence, as sometimes the only way for the immune system to eradicate pathogens is to sacrifice the infected cell. When the timing of cell death is inappropriate, however, havoc may ensue. So understanding the mechanisms that regulate cell death is just as important as understanding those responsible for the actual killing. A newly identified protein, described on page 190 of this issue by Irmler et al.2, and in Immunity by Shu et al.3, appears to act as a regulator of one of the principal ways by which immune mechanisms cause cell death — namely its induction by receptors belonging to the tumour necrosis factor (TNF)-receptor family4,5. This is a highly active research area, as exemplified by the fact that three other groups6,7,8, including my own, are shortly to publish on the same protein.

Death is a rather uncommon consequence of receptor triggering; usually, the process is concerned with the transmission of life-enhancing signals such as those that stimulate cell growth and division. Nonetheless, the emerging knowledge of induction of cell death by TNF receptors indicates that it happens in the same way as all other receptor-induced effects — that is, through a series of protein-protein bindings. The first involves the binding of specific ligands to the extracellular domains of the receptors. This is followed by sequential binding of cytoplasmic proteins to the intracellular domains of the receptors, leading eventually to activation of enzymatic function in some of these proteins. In the case of death induction, the activated enzymes include caspases, a family of cysteine proteases whose members occur in cells as latent precursors, becoming activated early in the process of programmed cell death and being central to its development9.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: The newly discovered regulatory protein, variously called FLIP2, Casper3, FLAME6, CASH7 and I-FLICE8 (here referred to as FLIP etc. for simplicity), may be involved in blocking the induction of cell death or in activating it.

References

  1. Jacobson, M. D., Weil, M. & Raff, M. C. Cell 88, 347–354 (1997).

    Google Scholar 

  2. Irmler, M. et al. Nature 388, 190–195 (1997).

    Article  ADS  CAS  Google Scholar 

  3. Shu, H.-B., Halpin, D. R. & Goeddel, D. V. Immunity 6, 751–763 (1997).

    Google Scholar 

  4. Smith, C. A., Farrah, T. & Goodwin, R. G. Cell 76, 959–962 (1994).

    Google Scholar 

  5. Nagata, S. Cell 88, 355–365 (1997).

    Google Scholar 

  6. Srinivasula, S. M. J. Biol. Chem. (in the press).

  7. Goltsev, Y. V. et al. (in the press).

  8. Hu, S. et al. (in the press).

  9. Henkart, P. A. Immunity 4, 195–201 (1996).

    Google Scholar 

  10. Wallach, D. Trends Biochem. Sci. 22, 107–109 (1997).

    Google Scholar 

  11. Thome, M. et al. Nature 386, 517–521 (1997).

    Article  ADS  CAS  Google Scholar 

  12. Bertin, J. et al. Proc. Natl. Acad. Sci. USA 94, 1172–1176 (1997).

    Google Scholar 

  13. Hu, S., Vincenz, C., Buller, M. & Dixit, V. M. J. Biol. Chem. 272, 9621–9624 (1997).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, 76100, Israel

    David Wallach

Authors
  1. David Wallach
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wallach, D. Placing death under control. Nature 388, 123–125 (1997). https://doi.org/10.1038/40516

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/40516

This article is cited by

Search

Advanced 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