ArticleScientific reports2018
DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform A function.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Induction and regulation of reversible suspended animation in C. elegans.Nature communications · 2026Article
- Induction and regulation of a reversible form of suspended animation inbioRxiv : the preprint server for biology · 2026Article
- Decreased Hsp90 activity protects against TDP-43 neurotoxicity in a C. elegans model of amyotrophic lateral sclerosis.PLoS genetics · 2024Article
- Dauer juvenile recovery transcriptome of two contrasting EMS mutants of the entomopathogenic nematode Heterorhabditis bacteriophora.World journal of microbiology & biotechnology · 2024Article
- Regulation of TFEB nuclear localization by HSP90AA1 promotes autophagy and longevity.Autophagy · 2023Article
- Transcellular chaperone signaling is an intercellular stress-response distinct from the HSF-1-mediated heat shock response.PLoS biology · 2023Article
- Organismal Roles of Hsp90.Biomolecules · 2023Review
- Exploiting inter-tissue stress signaling mechanisms to preserve organismal proteostasis during aging.Frontiers in physiology · 2023Review
- Recent Progress in Regulation of Aging by Insulin/IGF-1 Signaling inMolecules and cells · 2022Review
- Hsp90: From Cellular to Organismal Proteostasis.Cells · 2022Review
- Genes and Longevity of Lifespan.International journal of molecular sciences · 2022Review
- Insights Into the Links Between Proteostasis and Aging FromFrontiers in aging · 2022Review
- HSF-1: Guardian of the Proteome Through Integration of Longevity Signals to the Proteostatic Network.Frontiers in aging · 2022Review
- Article
- hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans.Scientific reports · 2021Article
- The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.Archives of toxicology · 2021Review
- Toxic stress-specific cytoprotective responses regulate learned behavioral decisions in C. elegans.BMC biology · 2021Article
- Enhanced Healthspan inFrontiers in pharmacology · 2021Article
- Healthspan Enhancement by Olive Polyphenols inInternational journal of molecular sciences · 2020Article
- Transcriptomics-Based Screening Identifies Pharmacological Inhibition of Hsp90 as a Means to Defer Aging.Cell reports · 2019Article
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3 authors.
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No grant is acknowledged in the PubMed record.
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.
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