期刊
CELLULAR SIGNALLING
卷 21, 期 1, 页码 143-150出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2008.10.001
关键词
HSP27; TRAF6; IL-1 beta; IKK ubiquitination
类别
资金
- Major State Basic Research Development Program of China [2002CB513000]
- National Nature Science Foundation of China [30770842, 30771979]
- Jiangsu Major Nature Science Foundation of High Education [06KJA31024]
Heat shock protein 27 (HSP27) is an ubiquitiously expressed protein, which has been mediated in various biological functions. Here, we present a novel mechanism utilized by HSP27 in regulating IL-1 beta induced NF-kappa B activation. Both over-expression and RNAi experiments indicate that HSP27 physically interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6) and promotes TRAF6 ubiquitination. Overexpressed HSP27 augments IL-1 beta induced TRAF6 ubiquitination and I kappa B kinase (IKK) activation. On the other hand, IL-1 beta stimulation reduces endogenous HSP27/TRAF6 association, but inhibiting HSP27 phosphorylation by using SB202190, an inhibitor of p38, and MAPKAPK2 RNAi increases HSP27/TRAF6 association and thereby enhances TRAF6 ubiquitination, IKK phosphorylation as well as NF-kappa B activation. Furthermore, co-transfection study shows that HSP27 S78/82A, two phosphorylated serine site deficient mutants, but not wild-type HSP27 (HSP27 WT) and HSP27 S15A mutant increases TRAF6 ubiquitination and thereby mediates IL-1 beta triggered IKK phosphorylation. Taken together, our data indicate that HSP27 regulates IL-1 beta triggered NF-kappa B activation via a feedback loop which includes the interaction between HSP27 phosphorylation and ability of HSP27 to bind with TRAF6. The findings of this study reveal a novel mechanism by which HSP27 controls cytokine stimulation. (C) 2008 Published by Elsevier Inc.
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