Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells

	Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells
	Yang, K; Shi, HX; Qi, R; Sun, SG; Tang, YJ; Zhang, BH; Wang, C
刊名	MOLECULAR BIOLOGY OF THE CELL
	2006
卷号	17 期号:3 页码:1461-1471
通讯作者	Wang, C (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,cwang01@sibs.ac.cn
英文摘要	Interferon regulatory factor 3 (IRF3) plays a crucial role in mediating cellular responses to virus intrusion. The protein kinase TBK1 is a key regulator inducing phosphorylation of IRF3. The regulatory mechanisms during IRF3 activation remain poorly characterized. In the present study, we have identified by yeast two-hybrid approach a specific interaction between IRF3 and chaperone heat-shock protein of 90 kDa (Hsp90). The C-terminal truncation mutant of Hsp90 is a strong dominant-negative inhibitor of IRF3 activation. Knockdown of endogenous Hsp90 by RNA interference attenuates IRF3 activation and its target gene expressions. Alternatively, Hsp90-specific inhibitor geldanamycin (GA) dramatically reduces expression of IRF3-regulated interferon-stimulated genes and abolishes the cytoplasm-to-nucleus translocation and DNA binding activity of IRF3 in Sendai virus-infected cells. Significantly, virus-induced IRF3 phosphorylation is blocked by GA, whereas GA does not affect the protein level of IRF3. In addition, TBK1 is found to be a client protein of Hsp90 in vivo. Treatment of 293 cells with GA interferes with the interaction of TBK1 and Hsp90, resulting in TBK1 destabilization and its subsequent proteasome-mediated degradation. Besides maintaining stability of TBK1, Hsp90 also forms a novel complex with TBK1 and IRF3, which brings TBK1 and IRF3 dynamically into proximity and facilitates signal transduction from TBK1 to IRF3. Our study uncovers an essential role of Hsp90 in the virus-induced activation of IRF3.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	NF-KAPPA-B ; TOLL-LIKE RECEPTORS ; HEAT-SHOCK PROTEINS ; DOUBLE-STRANDED-RNA ; MOLECULAR CHAPERONES ; IN-VIVO ; HEAT-SHOCK-PROTEIN-90 HSP90 ; GLUCOCORTICOID-RECEPTOR ; SIGNAL-TRANSDUCTION ; GENE-EXPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000235790100037
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1693]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Yang, K,Shi, HX,Qi, R,et al. Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells[J]. MOLECULAR BIOLOGY OF THE CELL,2006,17(3):1461-1471.
APA	Yang, K.,Shi, HX.,Qi, R.,Sun, SG.,Tang, YJ.,...&Wang, C.(2006).Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells.MOLECULAR BIOLOGY OF THE CELL,17(3),1461-1471.
MLA	Yang, K,et al."Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells".MOLECULAR BIOLOGY OF THE CELL 17.3(2006):1461-1471.