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

<div><p>MAP kinases are integral to the mechanisms by which cells respond to a wide variety of environmental stresses. In <i>Caenorhabditis elegans</i>, 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, <i>kreg-1</i> and <i>kreg-2</i>/<i>lys-3</i>, which are required for the defense against heavy metal stress. FOS-1 plays a critical role in the transcriptional repression of the <i>kreg-1</i> 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 <i>kreg</i> gene transcription, which modulates the stress response in <i>C. elegans</i>.</p>