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dc.contributor.author Somogyvári M
dc.contributor.author Gecse E
dc.contributor.author Sőti, Csaba
dc.date.accessioned 2018-10-01T09:51:27Z
dc.date.available 2018-10-01T09:51:27Z
dc.date.issued 2018
dc.identifier 85051667974
dc.identifier.citation pagination=12048, papers: 15; journalVolume=8; journalIssueNumber=1; journalTitle=SCIENTIFIC REPORTS;
dc.identifier.uri http://repo.lib.semmelweis.hu//handle/123456789/6426
dc.identifier.uri doi:10.1038/s41598-018-30592-6
dc.description.abstract The FOXO transcription factor family is a conserved regulator of longevity and the downstream target of insulin/insulin-like signaling. In Caenorhabditis elegans, the FOXO ortholog DAF-16A and D/F isoforms extend lifespan in daf-2 insulin-like receptor mutants. Here we identify the DAF-21/Hsp90 chaperone as a longevity regulator. We find that reducing DAF-21 capacity by daf-21(RNAi) initiated either at the beginning or at the end of larval development shortens wild-type lifespan. daf-21 knockdown employed from the beginning of larval development also decreases longevity of daf-2 mutant and daf-2 silenced nematodes. daf-16 loss-of-function mitigates the lifespan shortening effect of daf-21 silencing. We demonstrate that DAF-21 specifically promotes daf-2 and heat-shock induced nuclear translocation of DAF-16A as well as the induction of DAF-16A-specific mRNAs, without affecting DAF-16D/F localization and transcriptional function. DAF-21 is dispensable for the stability and nuclear import of DAF-16A, excluding a chaperone-client interaction and suggesting that DAF-21 regulates DAF-16A activation upstream of its cellular traffic. Finally, we show a selective requirement for DAF-21 to extend lifespan of DAF-16A, but not DAF-16D/F, transgenic daf-2 mutant strains. Our findings indicate a spatiotemporal determination of multiple DAF-21 roles in fertility, development and longevity and reveal an isoform-specific regulation of DAF-16 activity. © 2018, The Author(s).
dc.relation.ispartof urn:issn:2045-2322
dc.title DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function
dc.type Journal Article
dc.date.updated 2018-09-11T07:14:21Z
dc.language.rfc3066 en
dc.identifier.mtmt 3413840
dc.contributor.department SE/AOK/I/Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézet
dc.contributor.institution Semmelweis Egyetem


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