eak-3;eak-7

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Genetic mutants with eak-3, eak-7 alterations

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

Diet
OP50
Lifespan (days)
21.8
Lifespan change (compared to wild type)
42.48%
Phenotype
Lifespan extension in eak-7 null mutants does not require eak-3 activity.
Lifespan comparisons
Double mutant eak-3(mg344);eak-7(tm3188) has a lifespan of 21.8 days, while single mutant eak-3(mg344) has a lifespan of 15.8 days, single mutant eak-7(tm3188) has a lifespan of 20.1 days and wild type has a lifespan of 15.3 days.
Type of interaction
See methods
Synergistic (positive)
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)
19.8
Lifespan change (compared to wild type)
8.20%
Phenotype
Lifespan extension in eak-7 null mutants does not require eak-3 activity.
Lifespan comparisons
Double mutant eak-3(mg344);eak-7(tm3188) has a lifespan of 19.8 days, while single mutant eak-3(mg344) has a lifespan of 16.4 days, single mutant eak-7(tm3188) has a lifespan of 20.1 days and wild type has a lifespan of 18.3 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-3 eak-7

Entrez ID
Symbol
GenAge
Wormbase ID

190782
eak-3
View on GenAge (eak-3)
WBGene00022356

Enhancer of AKt-1 null

Locus: CELE_Y92C3A.3

Wormbase description: eak-3 encodes a protein required for the subset of DAF-16 functions controlling dauer development, but not for lifespan regulation; EAK-3 is expressed in XXX cells, and localizes to the plasma membrane, probably by N-terminal myristoylation; EAK-3 acts in a genetic pathway parallel to that of AKT-1, which may include AKT-2, EAK-4, EAK-6, or SDF-9; EAK-3 has no homologs outside of C. elegans itself, has 20% leucine-like residues, and has a single predicted coiled-coil domain; eak-3 mutants have a very weak dauer arrest phenotype at 25 deg. C., but strongly enhance the dauer arrest phenotype of akt-1(mg306), and enhances expression of the DAF-16 target sod-3; eak-3's dauer arrest and sod-3 overexpression phenotypes require DAF-12 and DAF-16; however, EAK-3 has no effect on lifespan.

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.

Orthologs of eak-3;eak-7 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of eak-3 in SynergyAge

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Species	Gene

Orthologs of eak-7 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5149