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Sci. STKE, 21 May 2002
Vol. 2002, Issue 133, p. pe27
[DOI: 10.1126/stke.2002.133.pe27]

PERSPECTIVES

TRAF1: Lord Without A RING

Juan M. Zapata* and John C. Reed*

The Burnham Institute, 10901 N. Torrey Pines Rd, La Jolla, CA 92037, USA.

Summary: 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-{alpha}, having increased T cell receptor (TCR)-dependent T cell proliferation rates in vitro. Also, these TRAF1-/- mice had increased sensitivity to TNF-{alpha}-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.

*Corresponding authors. E-mail: jzapata{at}burnham.org jreed{at}burnham.org

Citation: J. M. Zapata, J. C. Reed, TRAF1: Lord Without A RING. Sci. STKE 2002, pe27 (2002).

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