ife-2;skn-1

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Genetic mutants with ife-2, skn-1 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
24.86
Lifespan change (compared to wild type)
9.81%
Lifespan comparisons
Double mutant ife-2(RNAi);skn-1(zu135) has a lifespan of 24.86 days, while single mutant skn-1(zu135) has a lifespan of 20.29 days and wild type has a lifespan of 22.64 days.
Type of interaction
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Contains dependence
Citation
View abstract
Wang J et al., 2010, RNAi screening implicates a SKN-1-dependent transcriptional response in stress resistance and longevity deriving from translation inhibition. PLoS Genet. 6(8). pii: e1001048 20700440 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans SKN-1 (ortholog of mammalian Nrf1/2/3) is critical for oxidative stress resistance and promotes longevity under reduced insulin/IGF-1-like signaling (IIS), dietary restriction (DR), and normal conditions. SKN-1 inducibly activates genes involved in detoxification, protein homeostasis, and other functions in response to stress. Here we used genome-scale RNA interference (RNAi) screening to identify mechanisms that prevent inappropriate SKN-1 target gene expression under non-stressed conditions. We identified 41 genes for which knockdown leads to activation of a SKN-1 target gene (gcs-1) through skn-1-dependent or other mechanisms. These genes correspond to multiple cellular processes, including mRNA translation. Inhibition of translation is known to increase longevity and stress resistance and may be important for DR-induced lifespan extension. One model postulates that these effects derive from reduced energy needs, but various observations suggest that specific longevity pathways are involved. Here we show that translation initiation factor RNAi robustly induces SKN-1 target gene transcription and confers skn-1-dependent oxidative stress resistance. The accompanying increases in longevity are mediated largely through the activities of SKN-1 and the transcription factor DAF-16 (FOXO), which is required for longevity that derives from reduced IIS. Our results indicate that the SKN-1 detoxification gene network monitors various metabolic and regulatory processes. Interference with one of these processes, translation initiation, leads to a transcriptional response whereby SKN-1 promotes stress resistance and functions together with DAF-16 to extend lifespan. This stress response may be beneficial for coping with situations that are associated with reduced protein synthesis.

Search genes: ife-2 skn-1

Entrez ID
Symbol
GenAge
Wormbase ID

180393
ife-2
View on GenAge (ife-2)
WBGene00002060

Eukaryotic translation initiation factor 4E-2

Locus: CELE_R04A9.4

Wormbase description: ife-2 encodes a translation initiation factor 4F, cap-binding subunit (eIF-4E); by homology, IFE-2 is predicted to function in cap-dependent mRNA translation initiation; loss of ife-2 activity in adult animals extends lifespan.

Entrez ID
Symbol
GenAge
Wormbase ID

177343
skn-1
View on GenAge (skn-1)
WBGene00004804

Protein skinhead-1;SKiNhead

Locus: CELE_T19E7.2

Wormbase description: skn-1 encodes a bZip transcription factor orthologous to the mammalian Nrf (Nuclear factor-erythroid-related factor) transcription factors; during early embryogenesis, maternally provided SKN-1 is required for specification of the EMS blastomere, a mesendodermal precursor that gives rise to pharyngeal, muscle, and intestinal cells; later, during postembryonic development, SKN-1 functions in the p38 MAPK pathway to regulate the oxidative stress response and in parallel to DAF-16/FOXO in the DAF-2-mediated insulin/IGF-1-like signaling pathway to regulate adult lifespan; in vitro assays indicate that SKN-1 can be directly phosphorylated by the AKT-1, AKT-2, and SGK-1 kinases that lie downstream of DAF-2 in the insulin signaling pathway and in vivo experiments suggest that this phosphorylation is essential for regulation of SKN-1 nuclear accumulation and hence, transcriptional regulator activity; in the early embryo, SKN-1 is detected at highest levels in nuclei of the P1 blastomere and its descendants through the 8-cell stage of embryogenesis; later in embryogenesis, SKN-1 is observed in all hypodermal and intestinal nuclei, with reporter constructs indicating that intestinal expression begins as early as the 50-100-cell stage; in larvae and young adults, SKN-1::GFP reporters are expressed in the intestine and ASI neurons, with expression in intestinal nuclei enhanced under conditions of stress or reduced DAF-2 signaling.

Orthologs of ife-2;skn-1 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of ife-2 in SynergyAge

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Species	Gene

Orthologs of skn-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Nfe2
Mus musculus	Nfe2l2
Mus musculus	Nfe2l1