The checkpoint of death

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...