eak-7;hsf-1

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Genetic mutants with eak-7, hsf-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Diet
OP50
Lifespan (days)
11.1
Lifespan change (compared to wild type)
-24.49%
Phenotype
Eak-7 mutants live longer than wild-type animals, and this phenotype requires daf-16/FoxO, as well as the protein phosphatase 4 regulatory subunit SMK-1 and the heat-shock transcription factor HSF-1
Lifespan comparisons
Double mutant eak-7(tm3188);hsf-1(RNAi) has a lifespan of 11.1 days, while single mutant hsf-1(RNAi) has a lifespan of 10.8 days, single mutant eak-7(tm3188) has a lifespan of 19.4 days and wild type has a lifespan of 14.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Alam H et al., 2010, EAK-7 controls development and life span by regulating nuclear DAF-16/FoxO activity. Cell Metab. 12(1):30-41 20620993 Click here to select all mutants from this PubMed ID in the graph
Abstract
FoxO transcription factors control development and longevity in diverse species. Although FoxO regulation via changes in its subcellular localization is well established, little is known about how FoxO activity is regulated in the nucleus. Here, we show that the conserved C. elegans protein EAK-7 acts in parallel to the serine/threonine kinase AKT-1 to inhibit the FoxO transcription factor DAF-16. Loss of EAK-7 activity promotes diapause and longevity in a DAF-16/FoxO-dependent manner. Whereas akt-1 mutation activates DAF-16/FoxO by promoting its translocation from the cytoplasm to the nucleus, eak-7 mutation increases nuclear DAF-16/FoxO activity without influencing DAF-16/FoxO subcellular localization. Thus, EAK-7 and AKT-1 inhibit DAF-16/FoxO activity via distinct mechanisms. Our results implicate EAK-7 as a FoxO regulator and highlight the biological impact of a regulatory pathway that governs the activity of nuclear FoxO without altering its subcellular location.

Search genes: eak-7 hsf-1

Entrez ID
Symbol
GenAge
Wormbase ID

3564920
eak-7
View on GenAge (eak-7)
WBGene00010671

Enhancer of AKt-1 null

Locus: CELE_K08E7.1

Wormbase description: eak-7 encodes a conserved protein that contains a TLDc (TBC and LysM domain-containing) domain and an N-myristoylation motif; EAK-7 negatively regulates dauer formation and longevity by controlling the nuclear activity of the DAF-16/FoxO transcription factor; an EAK-7::GFP is widely expressed and localizes to the plasma membrane.

Entrez ID
Symbol
GenAge
Wormbase ID

173078
hsf-1
View on GenAge (hsf-1)
WBGene00002004

Heat Shock Factor

Locus: CELE_Y53C10A.12

Wormbase description: hsf-1 encodes the C. elegans heat-shock transcription factor ortholog; HSF-1 functions as a transcriptional regulator of stress-induced gene expression whose activity is required for heat-shock and proteotoxicity response, larval development, innate immunity, and regulation of adult lifespan; HSF-1 binds bovine calmodulin in vitro in a calcium-dependent manner.

Orthologs of eak-7;hsf-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of eak-7 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5149

Orthologs of hsf-1 in SynergyAge

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Species	Gene

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.