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© The Rockefeller University Press, 0021-9525/2003/8/533-a $5.00
The Journal of Cell Biology, Volume 162, Number 4, 533-a-533

The checkpoint of death

A cytoplasmic complex induces death if the NF-B pathway is not intact. Tschopp/Elsevier

Cells that fail to turn on a signaling pathway as instructed go on to commit suicide, according to Olivier Micheau and Jürg Tschopp (University of Lausanne, Switzerland). This checkpoint mechanism may ensure that aberrant signalers do not survive to form tumors or inappropriate cell types.

The mechanism explains how death and differentiation are coordinated from a single receptor, the TNF- receptor I (TNFR1). A host of proteins has been implicated in signaling from TNFR1, but these links have relied on overexpression experiments. On looking more carefully, the Swiss team found that a group of proteins formed complex I with TNFR1, and then later peeled away from TNFR1 and the plasma membrane to form the largely cytoplasmic complex II. Only in complex II were death domains available for the binding of other proteins such as FADD, with their recruitment leading to apoptosis.

But if complex I performed its signaling job correctly, the downstream NF-B pathway was turned on to produce FLIP_L. This protein shut down the proapoptotic activity of complex II, and thus cells survived.

If the cell has a defect in the NF-B pathway, says Tschopp, "this cell is probably a dangerous cell, and it needs to be eliminated." But intact signaling prevents this death, after a delay that allows sufficient time to make sure that the NF-B pathway is behaving correctly.

References:

Micheau, O., and J. Tschopp. 2003. Cell. 114:181–190.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 885K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?