The Caenorhabditis elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex

Ayuna Hattori; Tomoaki Mizuno; Mayuko Akamatsu; Naoki Hisamoto; Kunihiro Matsumoto

doi:10.1371/journal.pgen.1003315

The Caenorhabditis elegans JNK signaling pathway activates expression of stress response genes by derepressing the Fos/HDAC repressor complex

PLoS Genet. 2013;9(2):e1003315. doi: 10.1371/journal.pgen.1003315. Epub 2013 Feb 21.

Authors

Ayuna Hattori¹, Tomoaki Mizuno, Mayuko Akamatsu, Naoki Hisamoto, Kunihiro Matsumoto

Affiliation

¹ Department of Molecular Biology, Graduate School of Science, Nagoya University, Nagoya, Japan.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Caenorhabditis elegans Proteins* / physiology
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / physiology
Histone Deacetylases* / genetics
Histone Deacetylases* / metabolism
JNK Mitogen-Activated Protein Kinases / genetics
JNK Mitogen-Activated Protein Kinases / physiology
MAP Kinase Signaling System* / genetics
MAP Kinase Signaling System* / physiology
Phosphorylation
Promoter Regions, Genetic
Proto-Oncogene Proteins c-fos* / metabolism
Proto-Oncogene Proteins c-fos* / physiology
Stress, Physiological / genetics*
Transcriptional Activation

Substances

Caenorhabditis elegans Proteins
FOS-1 protein, C elegans
Proto-Oncogene Proteins c-fos
JNK Mitogen-Activated Protein Kinases
KGB-1 protein, C elegans
Histone Deacetylases

Grants and funding

This work was supported by the Grants-in-Aids for Scientific Research programs in Japan (TM, NH, and KM), the Takeda Science Foundation (TM and NH), and the Uehara Memorial Foundation (NH). AH was supported by JSPS Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.