Heat shock protein 27 mediated signaling in viral infection.
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, 6234-6243]. 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 NFκB-p65 occurs in a p38-dependent fashion [Rajaiya, J., et al. (2009) Mol. Vision 15, 2879-2889]. Herein, we report a novel role for HSP27 in an association of p38 with NFκB-p65. Immunoprecipitation assays of virus-infected but not mock-infected cells revealed a signaling complex including p38 and NFκB-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 NFκB-p65 and p38. By use of tagged p38 mutants, we found that amino acids 279-347 of p38 are necessary for the association of p38 with NFκB-p65. These studies strongly suggest that HSP27, p38, and NFκB-p65 form a signalosome in virus-infected cells and influence downstream expression of pro-inflammatory mediators.
Howe Laboratory, Mass Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Jaya
J
Rajaiya
Mohammad A
MA
Yousuf
Gurdeep
G
Singh
Heather
H
Stanish
James
J
Chodosh
D000258:Adenovirus Infections, Human / Q000378:metabolism* / Q000821:virology; D000260:Adenoviruses, Human / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D055551:HSP27 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018925:Chemokines; D055551:HSP27 Heat-Shock Proteins; D052002:NF-kappa B p50 Subunit; D048051:p38 Mitogen-Activated Protein Kinases