Heat Shock Protein 27 Mediated Signaling in Viral Infection

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• 作者：Jaya Rajaiya ; Mohammad A. Yousuf ; Gurdeep Singh ; Heather Stanish ; James Chodosh
• 刊名：Biochemistry
• 出版年：2012
• 出版时间：July 17, 2012
• 年：2012
• 卷：51
• 期：28
• 页码：5695-5702
• 全文大小：390K
• 年卷期：v.51,no.28(July 17, 2012)
• ISSN：1520-4995

文摘

Heat shock proteins (HSPs) play a critical role in many intracellular processes, including apoptosis and delivery of other proteins to intracellular compartments. Small HSPs have been shown previously to participate in many cellular functions, including IL-8 induction. Human adenovirus infection activates intracellular signaling, involving particularly the c-Src and mitogen-activated protein kinases [Natarajan, K., et al. (2003) J. Immunol. 170, 6234鈥?243]. HSP27 and MK2 are also phosphorylated, and c-Src, and its downstream targets, p38, ERK1/2, and c-Jun-terminal kinase (JNK), differentially mediate IL-8 and MCP-1 expression. Specifically, activation and translocation of transcription factor NF魏B-p65 occurs in a p38-dependent fashion [Rajaiya, J., et al. (2009) Mol. Vision 15, 2879鈥?889]. Herein, we report a novel role for HSP27 in an association of p38 with NF魏B-p65. Immunoprecipitation assays of virus-infected but not mock-infected cells revealed a signaling complex including p38 and NF魏B-p65. Transfection with HSP27 short interfering RNA (siRNA) but not scrambled RNA disrupted this association and reduced the level of IL-8 expression. Transfection with HSP27 siRNA also reduced the level of nuclear localization of NF魏B-p65 and p38. By use of tagged p38 mutants, we found that amino acids 279鈥?47 of p38 are necessary for the association of p38 with NF魏B-p65. These studies strongly suggest that HSP27, p38, and NF魏B-p65 form a signalosome in virus-infected cells and influence downstream expression of pro-inflammatory mediators.