The crosstalk of intracellular signaling pathways is extremely complex. Previous studies have shown that there is a potential crosstalk between MAPKs and NF-kappa B 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-kappa B 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-alpha-induced apoptosis. In addition, reduction of JNK activation attenuated HSP27 phosphorylation envoked by TNF-alpha, especially the phosphorylation of HSP27 at serine 78 residue. Our results also showed that suppression of INK activation reduced the degradation of I kappa B-alpha, but did not affect HOC phosphorylation upon TNF-alpha stimulation. Co-immunoprecipitation experiments demonstrated that JNK regulated the degradation of I kappa B-alpha through promoting the formation of HSP27/IKK/I kappa B-alpha ternary complex in response to TNF-alpha. Suppression of JNK activation hindered HSP27 phosphorylation at Ser78 residue and subsequently reduced the interaction between IKK and I kappa B-alpha. Taken together, our study suggests that through modulation the phosphorylation of HSP27, JNK plays an important roles in cell survival via regulating NF-kappa B signaling pathway. (C) 2014 Elsevier Inc. All rights reserved.