Perspective

TRAF1: Lord Without A RING

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Science's STKE  21 May 2002:
Vol. 2002, Issue 133, pp. pe27
DOI: 10.1126/stke.2002.133.pe27

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Abstract

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) constitute a family of adaptor proteins that associate with the cytosolic tail of particular TNF-family receptors (TNFR) and regulate cytokine signaling by linking TNFRs with downstream protein kinases, ubiquitin ligases, and other effector proteins. A total of six members of this family (TRAF1-6) have been identified in mammals. TRAF1 is unique among TRAFs because it lacks a RING finger domain present in TRAF2-6 that has been shown to be required for TRAF2- and TRAF6-mediated activities. TRAF1 also has the most restricted expression among TRAFs, and is found almost exclusively in activated lymphocytes, dendritic cells, and certain epithelia. Recent evidence obtained from TRAF1-/- mice shows that TRAF1-deficient T cells are hyper-responsive to TNF-α, having increased T cell receptor (TCR)-dependent T cell proliferation rates in vitro. Also, these TRAF1-/- mice had increased sensitivity to TNF-α-induced skin necrosis in vivo. These results support a role for TRAF1 as a negative regulator of signaling by certain TNF-family receptors. This review summarizes current knowledge about TRAF1, focusing on the new information provided by these TRAF1-deficient mice. Also, the pros and cons of TRAFs as potential targets for drug discovery are discussed.

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