daf-2;ftt-2

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Genetic mutants with daf-2, ftt-2 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
23.4
Lifespan change (compared to wild type)
23.81%
Phenotype
The strongest life span reduction was observed upon ftt-2 RNAi treatment on both daf-2 class mutants
Lifespan comparisons
Double mutant daf-2(e1365);ftt-2(RNAi) has a lifespan of 23.4 days, while single mutant ftt-2(RNAi) has a lifespan of 15.6 days, single mutant daf-2(e1365) has a lifespan of 31.3 days and wild type has a lifespan of 18.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Araiz C et al., 2008, 14-3-3 regulates life span by both DAF-16-dependent and -independent mechanisms in Caenorhabditis elegans. Exp Gerontol. 43(6):505-19 18423931 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans life span, stress resistance and metabolism are regulated by the Insulin/IGF-1/DAF-2/DAF-16 pathway. DAF-16, a member of FOXO/Forkhead transcription factor family, can be targeted by 14-3-3 proteins to promote stress resistance. We have identified a 14-3-3 C. elegans homolog which promotes life span by both DAF-2-dependent and -independent mechanisms and by an unexpected DAF-16-independent mechanism. Our results demonstrate that C. elegans 14-3-3 proteins modulate stress-responsive genes throughout adulthood. In conclusion, 14-3-3 can be considered as an acute stress-responsive regulator as well as a sustained modulator of the Insulin/IGF-1/DAF-2/DAF-16 regulatory pathway in promoting life expectancy of growing old worms.

Temperature °C
22.5
Diet
OP50
Lifespan (days)
11.4
Lifespan change (compared to wild type)
-40.00%
Phenotype
The ftt-2 RNAi treatments induced a significant life span reduction when applied to both daf-2 class mutants
Lifespan comparisons
Double mutant daf-2(e1365);ftt-2(RNAi) has a lifespan of 11.4 days, while single mutant ftt-2(RNAi) has a lifespan of 14.2 days, single mutant daf-2(e1365) has a lifespan of 28.6 days and wild type has a lifespan of 19.0 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Araiz C et al., 2008, 14-3-3 regulates life span by both DAF-16-dependent and -independent mechanisms in Caenorhabditis elegans. Exp Gerontol. 43(6):505-19 18423931 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans life span, stress resistance and metabolism are regulated by the Insulin/IGF-1/DAF-2/DAF-16 pathway. DAF-16, a member of FOXO/Forkhead transcription factor family, can be targeted by 14-3-3 proteins to promote stress resistance. We have identified a 14-3-3 C. elegans homolog which promotes life span by both DAF-2-dependent and -independent mechanisms and by an unexpected DAF-16-independent mechanism. Our results demonstrate that C. elegans 14-3-3 proteins modulate stress-responsive genes throughout adulthood. In conclusion, 14-3-3 can be considered as an acute stress-responsive regulator as well as a sustained modulator of the Insulin/IGF-1/DAF-2/DAF-16 regulatory pathway in promoting life expectancy of growing old worms.

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

Temperature °C
20
Lifespan (days)
38.0
Lifespan change (compared to wild type)
90.00%
Phenotype
Reducing 14-3-3 gene expression in a daf-2 mutant, which displays an increased life span, did not shorten life span
Lifespan comparisons
Double mutant daf-2(e1370);ftt-2(RNAi) has a lifespan of 38.0 days, while single mutant ftt-2(RNAi) has a lifespan of 17.0 days, single mutant daf-2(e1370) has a lifespan of 41.0 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Berdichevsky A et al., 2006, C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and extend life span. Cell. 125(6):1165-77 16777605 Click here to select all mutants from this PubMed ID in the graph
Abstract
The longevity of Caenorhabditis elegans is promoted by extra copies of the sir-2.1 gene in a manner dependent on the forkhead transcription factor DAF-16. We identify two C. elegans 14-3-3 proteins as SIR-2.1 binding partners and show that 14-3-3 genes are required for the life-span extension conferred by extra copies of sir-2.1. 14-3-3 proteins are also required for SIR-2.1-induced transcriptional activation of DAF-16 and stress resistance. Following heat stress, SIR-2.1 can bind DAF-16 in a 14-3-3-dependent manner. By contrast, low insulin-like signaling does not promote SIR-2.1/DAF-16 interaction, and sir-2.1 and the 14-3-3 genes are not required for the regulation of life span by the insulin-like signaling pathway. We propose the existence of a stress-dependent pathway in which SIR-2.1 and 14-3-3 act in parallel to the insulin-like pathway to activate DAF-16 and extend life span.

Temperature °C
25
Diet
NGM; HT115
Lifespan (days)
26.9
Lifespan change (compared to wild type)
61.08%
Lifespan comparisons
Double mutant daf-2(e1370);ftt-2(RNAi) has a lifespan of 26.9 days, while single mutant ftt-2(RNAi) has a lifespan of 15.8 days, single mutant daf-2(e1370) has a lifespan of 30.3 days and wild type has a lifespan of 16.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; HT115
Lifespan (days)
22.6
Lifespan change (compared to wild type)
34.52%
Lifespan comparisons
Double mutant daf-2(e1370);ftt-2(RNAi) has a lifespan of 22.6 days, while single mutant ftt-2(RNAi) has a lifespan of 16.3 days, single mutant daf-2(e1370) has a lifespan of 26.1 days and wild type has a lifespan of 16.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
25
Diet
NGM; HT115
Lifespan (days)
24.5
Lifespan change (compared to wild type)
45.83%
Lifespan comparisons
Double mutant daf-2(e1370);ftt-2(RNAi) has a lifespan of 24.5 days, while single mutant ftt-2(RNAi) has a lifespan of 16.1 days, single mutant daf-2(e1370) has a lifespan of 28.4 days and wild type has a lifespan of 16.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rizki G et al., 2011, The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO. PLoS Genet. 7(9):e1002235 21909281 Click here to select all mutants from this PubMed ID in the graph
Abstract
The conserved DAF-16/FOXO transcription factors and SIR-2.1/SIRT1 deacetylases are critical for diverse biological processes, particularly longevity and stress response; and complex regulation of DAF-16/FOXO by SIR-2.1/SIRT1 is central to appropriate biological outcomes. Caenorhabditis elegans Host Cell Factor 1 (HCF-1) is a longevity determinant previously shown to act as a co-repressor of DAF-16. We report here that HCF-1 represents an integral player in the regulatory loop linking SIR-2.1/SIRT1 and DAF-16/FOXO in both worms and mammals. Genetic analyses showed that hcf-1 acts downstream of sir-2.1 to influence lifespan and oxidative stress response in C. elegans. Gene expression profiling revealed a striking 80% overlap between the DAF-16 target genes responsive to hcf-1 mutation and sir-2.1 overexpression. Subsequent GO-term analyses of HCF-1 and SIR-2.1-coregulated DAF-16 targets suggested that HCF-1 and SIR-2.1 together regulate specific aspects of DAF-16-mediated transcription particularly important for aging and stress responses. Analogous to its role in regulating DAF-16/SIR-2.1 target genes in C. elegans, the mammalian HCF-1 also repressed the expression of several FOXO/SIRT1 target genes. Protein-protein association studies demonstrated that SIR-2.1/SIRT1 and HCF-1 form protein complexes in worms and mammalian cells, highlighting the conservation of their regulatory relationship. Our findings uncover a conserved interaction between the key longevity determinants SIR-2.1/SIRT1 and HCF-1, and they provide new insights into the complex regulation of FOXO proteins.

Temperature °C
22
Diet
NGM; OP50
Lifespan (days)
46.84
Lifespan change (compared to wild type)
208.16%
Phenotype
The ftt-2 RNAi knock down worms had a much shorter adult lifespan compared to the control RNAi worms. Interestingly, ftt-2 RNAi did not appear to affect the extended lifespan phenotype of daf-2(e1370) worms.
Lifespan comparisons
Double mutant daf-2(e1370);ftt-2(RNAi) has a lifespan of 46.84 days, while single mutant ftt-2(RNAi) has a lifespan of 11.66 days, single mutant daf-2(e1370) has a lifespan of 48.6 days and wild type has a lifespan of 15.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Li J et al., 2007, The 14-3-3 protein FTT-2 regulates DAF-16 in Caenorhabditis elegans. Dev Biol. 301(1):82-91 17098225 Click here to select all mutants from this PubMed ID in the graph
Abstract
The Caenorhabditis elegans daf-2/insulin-like signaling pathway is critical for regulating development, longevity, metabolism and stress resistance. We identified the 14-3-3 protein FTT-2 to be a new regulatory component of this pathway. We found that RNAi knock down of ftt-2 specifically enhanced the daf-2-mediated dauer formation phenotype. Furthermore, ftt-2 knock down caused the nuclear accumulation of DAF-16/FOXO, the forkhead transcription factor that is the major downstream effecter of daf-2/insulin-like signaling, and enhanced the transcriptional activities of DAF-16. In contrast to ftt-2, RNAi knock down of par-5/ftt-1, the only other gene predicted to encode a 14-3-3 protein in C. elegans, did not show any notable effect on dauer formation, DAF-16 localization, or DAF-16 downstream gene transcription, underscoring the functional specification of FTT-2 and PAR-5 despite their high sequence homology. Using co-immunoprecipitation, we revealed that FTT-2 formed a complex with GFP-fused DAF-16 in C. elegans. Our results indicate that FTT-2 binds to DAF-16 in C. elegans and regulates DAF-16 by sequestering it in the cytoplasm. A similar mechanism of regulation of FOXO by 14-3-3zeta has been reported in mammalian cells, highlighting the high degree of conservation of the daf-2/insulin-like signaling pathway.

Temperature °C
20
Diet
OP50
Lifespan (days)
18.5
Lifespan change (compared to wild type)
-2.12%
Phenotype
The strongest life span reduction was observed upon ftt-2 RNAi treatment on both daf-2 class mutants
Lifespan comparisons
Double mutant daf-2(e1370);ftt-2(RNAi) has a lifespan of 18.5 days, while single mutant ftt-2(RNAi) has a lifespan of 15.6 days, single mutant daf-2(e1370) has a lifespan of 28.6 days and wild type has a lifespan of 18.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Araiz C et al., 2008, 14-3-3 regulates life span by both DAF-16-dependent and -independent mechanisms in Caenorhabditis elegans. Exp Gerontol. 43(6):505-19 18423931 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans life span, stress resistance and metabolism are regulated by the Insulin/IGF-1/DAF-2/DAF-16 pathway. DAF-16, a member of FOXO/Forkhead transcription factor family, can be targeted by 14-3-3 proteins to promote stress resistance. We have identified a 14-3-3 C. elegans homolog which promotes life span by both DAF-2-dependent and -independent mechanisms and by an unexpected DAF-16-independent mechanism. Our results demonstrate that C. elegans 14-3-3 proteins modulate stress-responsive genes throughout adulthood. In conclusion, 14-3-3 can be considered as an acute stress-responsive regulator as well as a sustained modulator of the Insulin/IGF-1/DAF-2/DAF-16 regulatory pathway in promoting life expectancy of growing old worms.

Temperature °C
22.5
Diet
OP50
Lifespan (days)
8.4
Lifespan change (compared to wild type)
-55.79%
Phenotype
The strongest life span reduction was observed upon ftt-2 RNAi treatment on both daf-2 class mutants
Lifespan comparisons
Double mutant daf-2(e1370);ftt-2(RNAi) has a lifespan of 8.4 days, while single mutant ftt-2(RNAi) has a lifespan of 14.2 days, single mutant daf-2(e1370) has a lifespan of 26.1 days and wild type has a lifespan of 19.0 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Araiz C et al., 2008, 14-3-3 regulates life span by both DAF-16-dependent and -independent mechanisms in Caenorhabditis elegans. Exp Gerontol. 43(6):505-19 18423931 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caenorhabditis elegans life span, stress resistance and metabolism are regulated by the Insulin/IGF-1/DAF-2/DAF-16 pathway. DAF-16, a member of FOXO/Forkhead transcription factor family, can be targeted by 14-3-3 proteins to promote stress resistance. We have identified a 14-3-3 C. elegans homolog which promotes life span by both DAF-2-dependent and -independent mechanisms and by an unexpected DAF-16-independent mechanism. Our results demonstrate that C. elegans 14-3-3 proteins modulate stress-responsive genes throughout adulthood. In conclusion, 14-3-3 can be considered as an acute stress-responsive regulator as well as a sustained modulator of the Insulin/IGF-1/DAF-2/DAF-16 regulatory pathway in promoting life expectancy of growing old worms.

Search genes: daf-2 ftt-2

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Entrez ID
Symbol
GenAge
Wormbase ID

181348
ftt-2
View on GenAge (ftt-2)
WBGene00001502

14-3-3-like protein 2;Fourteen-Three-Three family

Locus: CELE_F52D10.3

Wormbase description: ftt-2 encodes a 14-3-3 protein; FTT-2 is required for regulating the localization of the product of YAP-1, a Yes-associated protein (Yap) homolog, between the cytoplasm and the nucleus.

Orthologs of daf-2;ftt-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	14-3-3zeta;InR
Mus musculus	Insr;Ywhaz
Mus musculus	Insr;Ywhaq
Mus musculus	Insr;Ywhab
Mus musculus	Igf1r;Ywhaz
Mus musculus	Igf1r;Ywhaq
Mus musculus	Igf1r;Ywhab
Mus musculus	Insrr;Ywhaz
Mus musculus	Insrr;Ywhaq
Mus musculus	Insrr;Ywhab
Mus musculus	Ywhaz;Insr
Mus musculus	Ywhaz;Igf1r
Mus musculus	Ywhaz;Insrr
Mus musculus	Ywhaq;Insr
Mus musculus	Ywhaq;Igf1r
Mus musculus	Ywhaq;Insrr
Mus musculus	Ywhab;Insr
Mus musculus	Ywhab;Igf1r
Mus musculus	Ywhab;Insrr

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of ftt-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	14-3-3zeta
Mus musculus	Ywhaz
Mus musculus	Ywhaq
Mus musculus	Ywhab