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Sci. Signal., 1 November 2011
Vol. 4, Issue 197, p. ra73
Limiting Persistent Inflammation
Interleukin-17 (IL-17) is a proinflammatory cytokine that is required for immune responses to extracellular pathogens, but it is also implicated in autoimmune disorders and inflammatory diseases. Signaling through the IL-17 receptor (IL-17R) requires the adaptor protein Act1 and leads to activation of the transcription factor NF-B. Shi et al. found that persistent stimulation of HeLa cells with IL-17 led to a loss of Act1 protein and inhibited responses of the cells to subsequent exposure to the cytokine. Stimulation with IL-17 led to phosphorylation, ubiquitination, and proteasomal degradation of Act1. The authors identified SCFβ-TrCP as the E3 ubiquitin ligase complex responsible for Act1 ubiquitination. SCFβ-TrCP is also required for IL-17–dependent degradation of the inhibitor of B (IB) protein to enable NF-B activation, positioning SCFβ-TrCP as both a positive and a negative regulator of IL-17 signaling.
Citation: P. Shi, S. Zhu, Y. Lin, Y. Liu, Y. Liu, Z. Chen, Y. Shi, Y. Qian, Persistent Stimulation with Interleukin-17 Desensitizes Cells Through SCFβ-TrCP-Mediated Degradation of Act1. Sci. Signal.4, ra73 (2011).
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 »