cst-1;daf-16

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Genetic mutants with cst-1, daf-16 alterations

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

Lifespan (days)
13.9
Lifespan change (compared to wild type)
-14.72%
Phenotype
DAF-16 acts downstream of CST-1 in life-span extension.
Lifespan comparisons
Double mutant cst-1(RNAi);daf-16(mgDf47) has a lifespan of 13.9 days, while single mutant daf-16(mgDf47) has a lifespan of 14.6 days and wild type has a lifespan of 16.3 days.
Type of interaction
See methods
Partially known monotony. Negative epistasis
Citation
View abstract
Lehtinen MK et al., 2006, A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 125(5):987-1001 16751106 Click here to select all mutants from this PubMed ID in the graph
Abstract
Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. Here, we demonstrate that the protein kinase MST1 mediates oxidative-stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. MST1 phosphorylates FOXO proteins at a conserved site within the forkhead domain that disrupts their interaction with 14-3-3 proteins, promotes FOXO nuclear translocation, and thereby induces cell death in neurons. We also extend the MST-FOXO signaling link to nematodes. Knockdown of the C. elegans MST1 ortholog CST-1 shortens life span and accelerates tissue aging, while overexpression of cst-1 promotes life span and delays aging. The cst-1-induced life-span extension occurs in a daf-16-dependent manner. The identification of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity.

Search genes: cst-1 daf-16

Entrez ID
Symbol
GenAge
Wormbase ID

180708
cst-1
View on GenAge (cst-1)
WBGene00017472

Serine/threonine-protein kinase cst-1 37kDa subunit

Locus: CELE_F14H12.4

Wormbase description: cst-1 encodes one of two C. elegans protein kinases orthologous to the MST (mammalian Ste20-like) kinases and Drosophila Hippo; CST-1 appears to play a role in the responses to oxidative stress and determination of adult lifespan; in regulating stress response and lifespan, CST-1 functions upstream of the DAF-16/FOXO transcription factor; CST-1 physically interacts with RSF-1, the C. elegans homolog of the Ras-association domain family protein 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.

Orthologs of cst-1;daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Stk3
Mus musculus	Foxo1;Stk3
Mus musculus	Foxo4;Stk3
Mus musculus	Foxo3;Stk3
Mus musculus	Foxo6;Stk4
Mus musculus	Foxo1;Stk4
Mus musculus	Foxo4;Stk4
Mus musculus	Foxo3;Stk4

Orthologs of cst-1 in SynergyAge

Show in SynergyAge
Species	Gene

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

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.