Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6

Zhili Rong, Long Cheng, Yongming Ren, Zhiyong Li, Yinghua Li, Xueni Li, Hongge Li, Xin Yuan Fu, Zhijie Chang

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Interleukin-17F (IL-17F), together with interleukin-17A (IL-17 or IL-17A), is a marker of TH17 cells, a new lineage of effector CD4+ T cells to contribute to pathogenesis of a growing list of autoimmune and inflammatory diseases, such as experimental autoimmune encephalitis (EAE) and collagen-induced arthritis (CIA). IL-17F, similar to IL-17A, was reported to employ interleukin-17 receptor (IL-17R or IL-17RA) for signaling but the downstream cascades remain largely elusive. Here we report that TRAF6 interacts with IL-17R and mediates ubiquitination of the receptor. We observed that IL-17F and IL-17A could induce IL-17R ubiquitination and DN-TRAF6, a dominant-negative mutant, could block IL-17F- but not IL-17A-triggered ubiquitination of IL-17R. Moreover, we showed that the ubiquitination of IL-17R was positively correlated with the downstream signaling, as evaluated by a luciferase reporter driven by a putative native promoter of 24p3, an IL-17 targeted gene. Our results indicate that ubiquitination of IL-17R mediated by TRAF6 plays a critical role in IL-17F signaling. This study, for the first time, reveals a possible molecular mechanism that the initiation of the IL-17F/IL-17R signaling pathway requires the receptor ubiquitination by TRAF6.

Original languageEnglish (US)
Pages (from-to)1514-1520
Number of pages7
JournalCellular Signalling
Volume19
Issue number7
DOIs
StatePublished - Jul 1 2007

Keywords

  • IL-17
  • IL-17F
  • IL-17R
  • signaling
  • T17 cells
  • TRAF6
  • ubiquitination

ASJC Scopus subject areas

  • Cell Biology

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    Rong, Z., Cheng, L., Ren, Y., Li, Z., Li, Y., Li, X., Li, H., Fu, X. Y., & Chang, Z. (2007). Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6. Cellular Signalling, 19(7), 1514-1520. https://doi.org/10.1016/j.cellsig.2007.01.025