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Sci. STKE, 22 February 2005
Vol. 2005, Issue 272, p. pe7
[DOI: 10.1126/stke.2722005pe7]

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TRAF2: A Double-Edged Sword?

Zong-Ping Xia and Zhijian J. Chen*

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9148, USA.

Abstract: Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor–associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K63)–linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism. Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a positive role in the canonical pathway that activates nuclear factor {kappa}B (NF-{kappa}B) through I{kappa}B kinase β (IKKβ), but a negative role in the noncanonical pathway that activates NF-{kappa}B through IKKα. These opposing roles of TRAF proteins may be linked to their ability to synthesize distinct forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K63 polyubiquitin chains, but is targeted to degradation by the proteasome when it is K48-polyubiquitinted by the NF-{kappa}B inhibitor A20. Thus, ubiquitin chains are dynamic switches that can influence signaling outputs in dramatically different ways.

*Corresponding author. E-mail: zhijian.chen{at}utsouthwestern.edu

Citation: Z.-P. Xia, Z. J. Chen, TRAF2: A Double-Edged Sword? Sci. STKE 2005, pe7 (2005).

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