The Caenorhabditis elegans JNK Signaling Pathway Activates Expression of Stress Response Genes by Derepressing the Fos/HDAC Repressor Complex

Map kinases are integral to the mechanisms by which cells respond to a wide variety of environmental stresses. in caenorhabditis elegans,the kgb-1 jnk signaling pathway regulates the response to heavy metal stress. in this study,we identified fos-1,a bzip transcription factor,as a target of kgb-1-mediated phosphorylation. we further identified two transcriptional targets of the kgb-1 pathway,kreg-1 and kreg-2/lys-3,which are required for the defense against heavy metal stress. fos-1 plays a critical role in the transcriptional repression of the kreg-1 gene by recruiting histone deacetylase (hdac) to its promoter. kgb-1 phosphorylation prevents fos-1 dimerization and promoter binding,resulting in promoter derepression. thus,hdac behaves as a co-repressor modulating fos-1-mediated transcriptional regulation. this study describes the direct link from jnk signaling,fos phosphorylation,and regulation of kreg gene transcription,which modulates the stress response in c. elegans. © 2013 hattori et al.