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Title of Paper:FOS-1 functions as a transcriptional activator downstream of the C. elegans JNK homolog KGB-1

Journal:Cellular signalling

Summary: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.

First Author:Zhe Zhang

Correspondence Author:Michael Shapira*

All the Authors:Limeng Liu,Kwame Twumasi-Boateng,Dena HS Block

Document Code:3

Impact Factor:4.01

DOI Number:10.1016/j.cellsig.2016.11.010

Translation or Not:No

Date of Publication:2017-01

Included Journals:SCI

Release Time:2017-01-01