daf-16;mpk-1

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Genetic mutants with daf-16, mpk-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)
11.4
Lifespan comparisons
Double mutant daf-16(mgDf50);mpk-1(RNAi) has a lifespan of 11.4 days, while single mutant daf-16(mgDf50) has a lifespan of 11.9 days.
Citation
View abstract
Okuyama T et al., 2010, The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like signaling in Caenorhabditis elegans. J Biol Chem. 285(39):30274-81 20624915 Click here to select all mutants from this PubMed ID in the graph
Abstract
It has not been determined yet whether the ERK-MAPK pathway regulates longevity of metazoans. Here, we show that the Caenorhabditis elegans ERK cascade promotes longevity through the two longevity-promoting transcription factors, SKN-1 and DAF-16. We find that RNAi of three genes, which constitute the ERK cascade (lin-45/RAF1, mek-2/MEK1/2, and mpk-1/ERK1/2), results in reduction of life span. Moreover, RNAi of lip-1, the gene encoding a MAPK phosphatase that inactivates MPK-1, increases life span. Epistasis analyses show that the ERK (MPK-1) cascade-mediated life span extension requires SKN-1, whose function is mediated, at least partly, through DAF-2/DAF-16 insulin-like signaling. MPK-1 phosphorylates SKN-1 on the key sites that are required for SKN-1 nuclear accumulation. Our results also show that one mechanism by which SKN-1 regulates insulin-like signaling is through the regulation of expression of insulin-like peptides. Our findings thus identify a novel ERK-MAPK-mediated signaling pathway that promotes longevity.

Search genes: daf-16 mpk-1

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

175545
mpk-1
View on GenAge (mpk-1)
WBGene00003401

Mitogen-activated protein kinase mpk-1

Locus: CELE_F43C1.2

Wormbase description: mpk-1 encodes a mitogen-activated protein (MAP) kinase an ERK ortholog functioning in vulval cell fate specification, cell migration/guidance, defense against bacterial infection, and other processes; in proximal germline, sperm-dependent physiological MPK-1 activation results in phosphorylation based inactivation of NOS-3, FEM-CUL-2-mediated degradation of TRA-1 and the promotion of membrane organization during oogenesis; mpk-1 affect LET-60(Ras)-mediated induction of vulval cell fates, larval viability, morphology of the male spicules; both LIN-1 and LIN-31 act genetically downstream of mpk-1 with respect to vulval induction; MPK-1 is necessary for pachytene cell organization; mpk-1 mutants display germ cells arrested in pachytene; MPK-1 is necessary for the progression from distal to proximal pachytene; MPK-1 promotes pachytene progression, with the rise in dpMPK-1 triggering a transition from a distal pachytene to a proximal pachytene subtype; MPK-1 functions in the germline for meiotic prophase progression and gametogenesis; MPK-1 ERK signaling is necessary for the male germ cell fate; MPK-1 ERK has the nonessential function of promoting the proliferative germ cell fate; mpk-1 acts in combination with mek-2 to permit germ cell exit from the pachytene stage of first meiotic prophase; MPK-1 activation is temporally/spatially dynamic compared to relatively constant levels of total MPK-1.

Orthologs of daf-16;mpk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Mapk1
Mus musculus	Foxo6;Mapk3
Mus musculus	Foxo1;Mapk1
Mus musculus	Foxo1;Mapk3
Mus musculus	Foxo4;Mapk1
Mus musculus	Foxo4;Mapk3
Mus musculus	Foxo3;Mapk1
Mus musculus	Foxo3;Mapk3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of mpk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	rl
Mus musculus	Mapk1
Mus musculus	Mapk3