Glycogen synthase kinase 3 beta ubiquitination by TRAF6 regulates TLR3-mediated pro-inflammatory cytokine production
- 등재 SCIE, SCOPUS
- 발행기관 NATURE PUBLISHING GROUP
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000115653
- 본문언어 영어
- Published As http://dx.doi.org/10.1038/ncomms7765
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
TRAF6 is critical for the production of inflammatory cytokines in various TLR-mediated signalling pathways. However, it is poorly understood how TRAF6 regulates TLR3 responses. Here we demonstrate that GSK3 beta interacts with TRAF6 and positively regulates the TLR3-mediated signalling. Suppression of GSK3 beta expression or its kinase activity drastically reduces the production of inflammatory cytokines and the induction of c-Fos by decreasing ERK and p38 phosphorylation. GSK3 beta physically associates with TRAF6 in a TLR3 ligand poly I:C-dependent manner. TRAF6 is determined to be a direct E3 ligase for GSK3 beta, and TRAF6-mediated GSK3 beta ubiquitination is essential for poly I:C-dependent cytokine production by promoting the TLR3 adaptor protein TRIF-assembled signalling complex.
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