title: FOS-1 functions as a transcriptional activator downstream of the C. elegans JNK homolog KGB-1.
abstract: JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK-homolog KGB-1 plays essential roles in protection from heavy metals and protein folding stress. However, the contributions of KGB-1 are age-dependent, providing protection in larvae, but reducing stress resistance and shortening lifespan in adults. Attenuation of DAF-16 was linked to the detrimental contributions of KGB-1 in adults, but its involvement in KGB-1-dependent protection in larvae remains unclear. To characterize age-dependent contributions of KGB-1, we used microarray analysis to measure gene expression following KGB-1 activation either in developing larvae or in adults, achieved by knocking down its negative phosphatase regulator vhp-1. This revealed a robust KGB-1 regulon, most of which consisting of genes induced following KGB-1 activation regardless of age; a smaller number of genes was regulated in an age-dependent manner. We found that the bZIP transcription factor FOS-1 was essential for age-invariant KGB-1-dependent gene induction, but not for age-dependent expression. The latter was more affected by DAF-16, which was further found to be required for KGB-1-dependent cadmium resistance in larvae. Our results identify FOS-1 as a transcriptional activator mediating age-invariant contributions of KGB-1, including a regulatory loop of KGB-1 signaling, but also stress the importance of DAF-16 as a mediator of age-dependent contributions.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Limeng
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Graduate Group in Microbiology, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kwame
authors.initials: K
authors.lastname: Twumasi-Boateng
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Dena H S
authors.initials: DH
authors.lastname: Block
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Graduate Group in Microbiology, University of California Berkeley, Berkeley, CA 94720, USA. Electronic address: mshapira@berkeley.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Shapira
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D002104:Cadmium / Q000633:toxicity; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D063990:Gene Ontology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D018085:Regulon / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C520083:FOS-1 protein, C elegans; D016760:Proto-Oncogene Proteins c-fos; D015534:Trans-Activators; D002104:Cadmium; D048031:JNK Mitogen-Activated Protein Kinases; C524496:KGB-1 protein, C elegans
keywords: Antagonistic pleiotropy; Cadmium; DAF-16; FOS-1; JNK; KGB-1