title: Crosstalk between JNK and NF-κB signaling pathways via HSP27 phosphorylation in HepG2 cells.
abstract: The crosstalk of intracellular signaling pathways is extremely complex. Previous studies have shown that there is a potential crosstalk between MAPKs and NF-κB signaling pathways. It has been reported that JNK regulates cell survival under some conditions. But the molecular mechanism through which JNK regulates cell survival is still unclear. In the present study, we hypothesized that there was a crosstalk between JNK and NF-κB signaling pathway regulating cell survival and HSP27 phosphorylation mediates such a crosstalk. Our data showed that in HepG2 cells, suppression of JNK activation by a specific inhibitor or overexpression of JNK inactive mutant enhanced TNF-α-induced apoptosis. In addition, reduction of JNK activation attenuated HSP27 phosphorylation envoked by TNF-α, especially the phosphorylation of HSP27 at serine 78 residue. Our results also showed that suppression of JNK activation reduced the degradation of IκB-α, but did not affect IKK phosphorylation upon TNF-α stimulation. Co-immunoprecipitation experiments demonstrated that JNK regulated the degradation of IκB-α through promoting the formation of HSP27/IKK/IκB-α ternary complex in response to TNF-α. Suppression of JNK activation hindered HSP27 phosphorylation at Ser78 residue and subsequently reduced the interaction between IKK and IκB-α. Taken together, our study suggests that through modulation the phosphorylation of HSP27, JNK plays an important roles in cell survival via regulating NF-κB signaling pathway.
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu, Anhui, PR China.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Yimiao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Lan
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, PR China. Electronic address: lanluo@nju.edu.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, PR China. Electronic address: yinzhimin@njnu.edu.cn.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yin
mesh_terms: D017209:Apoptosis; D004789:Enzyme Activation; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: Apoptosis; HSP27 phosphorylation; JNK; NF-κB