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PQM-1 Complements DAF-16 as a Key Transcriptional Regulator of DAF-2-Mediated Development and Longevity

Author(s): Tepper, Ronald G; Ashraf, Jasmine; Kaletsky, Rachel; Kleemann, Gunnar; Murphy, Coleen T; et al

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dc.contributor.authorTepper, Ronald G-
dc.contributor.authorAshraf, Jasmine-
dc.contributor.authorKaletsky, Rachel-
dc.contributor.authorKleemann, Gunnar-
dc.contributor.authorMurphy, Coleen T-
dc.contributor.authorBussemaker, Harmen J-
dc.date.accessioned2023-12-12T15:02:01Z-
dc.date.available2023-12-12T15:02:01Z-
dc.date.issued2013-08-01en_US
dc.identifier.citationTepper, Ronald G, Ashraf, Jasmine, Kaletsky, Rachel, Kleemann, Gunnar, Murphy, Coleen T, Bussemaker, Harmen J. (2013). PQM-1 Complements DAF-16 as a Key Transcriptional Regulator of DAF-2-Mediated Development and Longevity. Cell, 154 (3), 676 - 690. doi:10.1016/j.cell.2013.07.006en_US
dc.identifier.issn0092-8674-
dc.identifier.urihttp://arks.princeton.edu/ark:/88435/pr1kp7tr30-
dc.description.abstractReduced insulin/IGF-1-like signaling (IIS) extends C. elegans lifespan by upregulating stress response (Class I) and downregulating other (Class II) genes through a mechanism that depends on the conserved transcription factor DAF-16/FOXO. By integrating genomewide mRNA expression responsiveness to DAF-16 with genomewide in vivo binding data for a compendium of transcription factors, we discovered that PQM-1 is the elusive transcriptional activator that directly controls development (Class II) genes by binding to the DAF-16 associated element (DAE). DAF-16 directly regulates Class I genes only, through the DAF-16 binding element (DBE). Loss of PQM-1 suppresses daf-2 longevity and further slows development. Surprisingly, the nuclear localization of PQM-1 and DAF-16 is controlled by IIS in opposite ways, and was also found to be mutually antagonistic. We observe progressive loss of nuclear PQM-1 with age, explaining declining expression of PQM-1 targets. Together, our data suggest an elegant mechanism for balancing stress response and development.en_US
dc.format.extent676 - 690en_US
dc.language.isoen_USen_US
dc.relation.ispartofCellen_US
dc.rightsAuthor's manuscripten_US
dc.titlePQM-1 Complements DAF-16 as a Key Transcriptional Regulator of DAF-2-Mediated Development and Longevityen_US
dc.typeJournal Articleen_US
dc.identifier.doidoi:10.1016/j.cell.2013.07.006-
pu.type.symplectichttp://www.symplectic.co.uk/publications/atom-terms/1.0/journal-articleen_US

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