Regulation of c-Jun N-terminus kinase activity by Daxx after hydrogen peroxide treatment

Abstract

Daxx has been implicated in the regulation of c-Jun N-terminus Kinase (JNK) activity and apoptosis, however, data on Daxx effect on apoptosis are controversial. According to many reports, Daxx participates in activation of JNK and acts as a proapoptotic protein, while others state that Daxx may block activation of JNK and apoptosis. In this study, we investigated hydrogen peroxide-mediated JNK activation and its dependence on the expression level of Daxx protein. Our data show that Daxx overexpression does not effect JNK activation. We have also found that cell lines generated from Daxx gene knockout mice are still capable to respond to H2O2 treatment by JNK activation. Reconstitution of wild type Daxx protein expression in Daxx knocked out cells prolongs H2O2-induced JNK activation. Moreover, expression of Daxx mutant consisting of its C-terminus dramatically reduces JNK stimulation. Our findings provide an evidence that upon exposure to hydrogen peroxide Daxx prolongs JNK activation dynamics, and the C-terminus of Daxx alone is able to decrease JNK activation and probably participates in the regulation of JNK activation. Keywords: MAPK, mitogen activated protein kinase; ASK1, apoptosis signal regulating kinase 1; JNK, c-Jun N-terminal kinase; ROS, reactive oxygen species