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 Citations (Scopus)

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

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Interleukin-17 Receptors
TNF Receptor-Associated Factor 6
Interleukin-17
Ubiquitination
Th17 Cells
Experimental Arthritis

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6. / Rong, Zhili; Cheng, Long; Ren, Yongming; Li, Zhiyong; Li, Yinghua; Li, Xueni; Li, Hongge; Fu, Xin Yuan; Chang, Zhijie.

In: Cellular Signalling, Vol. 19, No. 7, 07.2007, p. 1514-1520.

Research output: Contribution to journalArticle

Rong, Z, Cheng, L, Ren, Y, Li, Z, Li, Y, Li, X, Li, H, Fu, XY & Chang, Z 2007, 'Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6', Cellular Signalling, vol. 19, no. 7, pp. 1514-1520. https://doi.org/10.1016/j.cellsig.2007.01.025
Rong, Zhili ; Cheng, Long ; Ren, Yongming ; Li, Zhiyong ; Li, Yinghua ; Li, Xueni ; Li, Hongge ; Fu, Xin Yuan ; Chang, Zhijie. / Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6. In: Cellular Signalling. 2007 ; Vol. 19, No. 7. pp. 1514-1520.
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