akt-2;eak-7

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Genetic mutants with akt-2, eak-7 alterations

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

Diet
OP50
Lifespan (days)
25.7
Lifespan change (compared to wild type)
74.83%
Phenotype
Eak-7 null mutation enhances the lifespan extension observed in akt-2 null mutants.
Lifespan comparisons
Double mutant akt-2(ok393);eak-7(tm3188) has a lifespan of 25.7 days, while single mutant akt-2(ok393) has a lifespan of 21.8 days, single mutant eak-7(tm3188) has a lifespan of 18.0 days and wild type has a lifespan of 14.7 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)
24.3
Lifespan change (compared to wild type)
62.00%
Phenotype
Eak-7 null mutation enhances the lifespan extension observed in akt-2 null mutants.
Lifespan comparisons
Double mutant akt-2(ok393);eak-7(tm3188) has a lifespan of 24.3 days, while single mutant akt-2(ok393) has a lifespan of 19.1 days, single mutant eak-7(tm3188) has a lifespan of 17.8 days and wild type has a lifespan of 15.0 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.

Search genes: akt-2 eak-7

Entrez ID
Symbol
GenAge
Wormbase ID

181524
akt-2
View on GenAge (akt-2)
WBGene00000103

Serine/threonine-protein kinase akt-2

Locus: CELE_F28H6.1

Wormbase description: akt-2 encodes a homolog of the serine/threonine kinase Akt/PKB, AKT-2, that is required for progression through the dauer stage of development and for the negative regulation of adult lifespan; inactivation of akt-2 causes animals to arrest constitutively at the dauer stage, while having an increased life span; widely expressed, AKT-2 is activated by the phospholipid products of phosphoinositide 3-kinase AGE-1/PI3K and by PDK-1, a homolog of vertebrate 3-phosphoinositide-dependent kinase-1 (PDK-1) Normal akt-2 (and akt-1) activity is required for excess pdk-1 activity to suppress the dauer-arrest phenotype of age-1, indicating that the 3-phosphoinositide-dependent kinase-1 homolog PDK-1 transduces signals from AGE-1 to AKT-2 (and AKT-1); conversely, the akt-2 loss-of-function phenotype is suppressed by daf-16 null mutations, indicating that the Fork head transcription factor DAF-16 is downstream of AKT-2 (and AKT-1), and that AKT-1 and AKT-2 act primarily to antagonize DAF-16.

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 akt-2;eak-7 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Akt1;CG5149

Orthologs of akt-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Akt1
Mus musculus	Akt1
Mus musculus	Akt2
Mus musculus	Akt3

Orthologs of eak-7 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5149