eak-7;rle-1

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Genetic mutants with eak-7, rle-1 alterations

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

Diet
OP50
Lifespan (days)
15.1
Lifespan change (compared to wild type)
2.72%
Phenotype
The rle-1(tm2447) mutation does not extend lifespan.
Lifespan comparisons
Double mutant eak-7(tm3188);rle-1(tm2447) has a lifespan of 15.1 days, while single mutant rle-1(tm2447) has a lifespan of 14.2 days, single mutant eak-7(tm3188) has a lifespan of 17.5 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.

Diet
OP50
Lifespan (days)
13.1
Lifespan change (compared to wild type)
-12.08%
Phenotype
The rle-1(tm2447) mutation does not extend lifespan.
Lifespan comparisons
Double mutant eak-7(tm3188);rle-1(tm2447) has a lifespan of 13.1 days, while single mutant rle-1(tm2447) has a lifespan of 12.0 days, single mutant eak-7(tm3188) has a lifespan of 17.2 days and wild type has a lifespan of 14.9 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 rle-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

176525
rle-1
View on GenAge (rle-1)
WBGene00010923

Regulation of longevity by E3 ubiquitin-protein ligase

Locus: CELE_M142.6

Wormbase description: none available

Orthologs of eak-7;rle-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 rle-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Rc3h2
Mus musculus	Rc3h1