mpk-1;skn-1

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Genetic mutants with mpk-1, 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)
16.36
Lifespan comparisons
Double mutant mpk-1(RNAi);skn-1(zu135) has a lifespan of 16.36 days, while single mutant skn-1(zu135) has a lifespan of 16.36 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.

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

Temperature °C
20
Diet
NGM
Lifespan (days)
12.04
Lifespan comparisons
Double mutant mpk-1(RNAi);skn-1(zu67) has a lifespan of 12.04 days, while single mutant skn-1(zu67) has a lifespan of 13.18 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: mpk-1 skn-1

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.

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 mpk-1;skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Mapk1;Nfe2
Mus musculus	Mapk1;Nfe2l2
Mus musculus	Mapk1;Nfe2l1
Mus musculus	Mapk3;Nfe2
Mus musculus	Mapk3;Nfe2l2
Mus musculus	Mapk3;Nfe2l1
Mus musculus	Nfe2;Mapk1
Mus musculus	Nfe2;Mapk3
Mus musculus	Nfe2l2;Mapk1
Mus musculus	Nfe2l2;Mapk3
Mus musculus	Nfe2l1;Mapk1
Mus musculus	Nfe2l1;Mapk3

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

Orthologs of skn-1 in SynergyAge

Show in SynergyAge
Species	Gene

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