Life or Death, RIP Switches TNF Receptor Signals

Science's STKE  11 Jan 2000:
Vol. 2000, Issue 14, pp. tw2
DOI: 10.1126/stke.2000.14.tw2

In T cells, tumor necrosis factor (TNF) can cause proliferation or apoptosis, depending on whether the T cell has been exposed to the cytokine interleukin-2 (IL-2). Pimentel-Muiños and Seed present evidence that the critical difference in such TNF receptor signals is the presence of the death domain–containing serine-threonine kinase RIP. Although TNFR2 does not have a death domain (through which TNFR1 associates with RIP), when expression of RIP is increased in response to IL-2, stimulation of TNFR2 caused apoptosis. The TNF receptors also produce an antiapoptotic signal through the transcription factor NF-κB. The authors point out that balance of the signals promoting or repressing cell death from the TNF receptors are very different depending on the cell type or, in the case of T cells, their state of activation.

Pimentel-Muiños, F. and Seed, B. (1999) Regulated commitment of TNF receptor signaling: A molecular switch for death or activation. Immunity 11: 783-793. [Online Journal]