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Sci. Signal., 13 October 2009
Vol. 2, Issue 92, p. ra63
[DOI: 10.1126/scisignal.2000382]

RESEARCH ARTICLES

Editor's Summary

Acting Out a New Role
Interleukin-17A (IL-17A) is the founding member of a family of proinflammatory cytokines implicated in the development of autoimmunity and the fight against microbial infection. IL-17 signaling, which is mediated by a number of IL-17 receptor (IL-17R) complexes (see the Perspective by Levin), depends on TRAF6, a scaffold protein and E3 ubiquitin ligase, and activates the transcription factor NF-{kappa}B. TRAF6 is recruited to IL-17Rs through another adaptor protein, Act1. Liu et al. now show that Act1 is also a member of the U-box family of E3 enzymes and that its ubiquitin ligase activity is required for IL-17R signaling. In response to IL-17, TRAF6 was recruited to Act1 and underwent Lys63-mediated ubiquitination, a process that was required for the activation of NF-{kappa}B. A mutant form of TRAF6 lacking the residue targeted by ubiquitin failed to support IL-17–mediated activation of NF-{kappa}B in TRAF6-deficient cells. Together, these data identify TRAF6 as a substrate of Act1 and suggest that sequential ubiquitination events regulate IL-17–induced inflammation.

Citation: C. Liu, W. Qian, Y. Qian, N. V. Giltiay, Y. Lu, S. Swaidani, S. Misra, L. Deng, Z. J. Chen, X. Li, Act1, a U-box E3 Ubiquitin Ligase for IL-17 Signaling. Sci. Signal. 2, ra63 (2009).

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