eak-7;smk-1

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Genetic mutants with eak-7, smk-1 alterations

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

Diet
OP50
Lifespan (days)
14.5
Lifespan change (compared to wild type)
9.85%
Phenotype
The lifespan extension phenotype of eak-7 mutants is suppressed by RNAi of smk-1.
Lifespan comparisons
Double mutant eak-7(tm3188);smk-1(RNAi) has a lifespan of 14.5 days, while single mutant smk-1(RNAi) has a lifespan of 11.6 days, single mutant eak-7(tm3188) has a lifespan of 18.1 days and wild type has a lifespan of 13.2 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 smk-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

179243
smk-1
View on GenAge (smk-1)
WBGene00018285

SMEK (Dictyostelium Suppressor of MEK null) homolog

Locus: CELE_F41E6.4

Wormbase description: smk-1 encodes a novel, evolutionarily conserved protein that is orthologous to the mammalian and Dictyostelium discoideum SMEK (suppressor of MEK null) proteins; smk-1 activity is essential for several aspects of DAF-16-mediated longevity namely, the defense response to pathogenic bacteria and increased resistance to oxidative and UV-induced damage; in regulating DAF-16 activity, SMK-1 appears to act by affecting the transcription of DAF-16 target genes, such as sod-3, ctl-1, and lys-8; SMK-1 is present in the nucleus of intestinal cells, many head and tail neurons, and some hypodermal cells throughout development.

Orthologs of eak-7;smk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5149;flfl

Orthologs of eak-7 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CG5149

Orthologs of smk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	flfl
Mus musculus	4932429P05Rik
Mus musculus	4930415L06Rik
Mus musculus	Ppp4r3a
Mus musculus	Ppp4r3b

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.