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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-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-B. A mutant form of TRAF6 lacking the residue targeted by ubiquitin failed to support IL-17–mediated activation of NF-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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RESEARCH ARTICLES
Caini Liu, Shadi Swaidani, Wen Qian, Zizhen Kang, Paige Sun, Yue Han, Chenhui Wang, Muhammet Fatih Gulen, Weiguo Yin, Chunjiang Zhang, Paul L. Fox, Mark Aronica, Thomas A. Hamilton, Saurav Misra, Junpeng Deng, and Xiaoxia Li (1 November 2011) Sci. Signal.4 (197), ra72.
[DOI: 10.1126/scisignal.2001843] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
Kristen L. Mueller (5 April 2011) Sci. Signal.4 (167), ec96.
[DOI: 10.1126/scisignal.4167ec96] |Abstract »
PERSPECTIVES
Steven D. Levin (13 October 2009) Sci. Signal.2 (92), pe64.
[DOI: 10.1126/scisignal.292pe64] |Abstract »|Full Text »|PDF »
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Fang Shen, Nan Li, Padmaja Gade, Dhananjaya V. Kalvakolanu, Timothy Weibley, Brad Doble, James R. Woodgett, Troy D. Wood, and Sarah L. Gaffen (24 February 2009) Sci. Signal.2 (59), ra8.
[DOI: 10.1126/scisignal.2000066] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »
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IL-17 Receptor Signaling: Ubiquitin Gets In On the Act.
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-
