Runner Up: Divining the death wish

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Science  20 Dec 1996:
Vol. 274, Issue 5295, pp. 1988
DOI: 10.1126/science.274.5295.1988i

Every cell contains a suicide program, activated when the good of the organism demands the sacrifice of individual cells. This year, researchers made new leaps in decoding this genetic self-destruct program, helping to clarify the normal process of programmed cell death, or apoptosis, and offering new understanding of diseases in which it goes awry.

Some of the executioner molecules inside cells were already known to belong to a family of protein-degrading enzymes known as ICE-like proteases. Turning on one ICE allows it to awaken others, unleashing an army of proteases that chop up proteins and kill the cell. But what signal turns on that first ICE? This year, researchers found that in at least some cases, the pathway is surprisingly short: When a cell surface receptor called Fas receives an extracellular death signal, it bypasses the usual long chain of signaling enzymes and immediately grabs and apparently activates an ICE enzyme.

Another death inducer, tumor necrosis factor, deals a weaker blow, and this year researchers found out why: TNF triggers a less direct suicide pathway and at the same time activates a competing pathway that prevents death. The fate of the cell depends on which signaling cascade wins the race. All this has practical import: It may one day help researchers learn to sabotage the anti-death pathway in cancer cells, or block the suicide pathway in brains after stroke.

Scuicide mission.

An ICE protease triggers cells' self-destruct program.



News Stories:

  • M. Barinaga, “Forging a Path to Cell Death,” Science, 9 August 1996, p. 735.

  • M. Barinaga, “Life-Death Balance Within the Cell,” Science, 1 November 1996, p. 724.

Research Papers:

  • A. A. Beg and D. Baltimore, “An Essential Role for NF-κB in Preventing TNF-α-Induced Cell Death,” Science, 1 November 1996, p. 782.

  • M. P. Boldin, T. M. Goncharov, Y. V. Goltsev, D. Wallach, “Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor-Induced Cell Death,” Cell 85, 803 (14 June 1996).

  • M. Muzio, A. M. Chinnaiyan, F. C. Kischkel, et al., “FLICE, a Novel FADD-Homologous ICE/CED-3-like Protease, Is Recruited to the CD95 (Fas/Apo-1) Death-Inducing Signaling Complex,” Cell 85, 817 (14 June 1996).

  • D. J. Van Antwerp et al., “Suppression of TNF-α-Induced Apoptosis by NF-κB,” Science, 1 November 1996, p. 787.

  • C.-Y. Wang, M. W. Mayo, A. S. Baldwin Jr., “TNF- and Cancer Therapy-Induced Apoptosis: Potentiation by Inhibition of NF-κB,” Science, 1 November 1996, p. 784.

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