daf-16;ftt-2

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Genetic mutants with daf-16, ftt-2 alterations

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

Temperature °C
20
Lifespan (days)
17.7
Lifespan change (compared to wild type)
-6.35%
Phenotype
Similar to SIR-2.1 and DAF-16, overexpression of the 14-3-3 proteins can extend life span.
Lifespan comparisons
Double mutant daf-16(RNAi);ftt-2(OE) has a lifespan of 17.7 days, while single mutant ftt-2(OE) has a lifespan of 24.4 days, single mutant daf-16(RNAi) has a lifespan of 14.3 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
Wang Y et al., 2006, C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech Ageing Dev. 127(9):741-7 16860373 Click here to select all mutants from this PubMed ID in the graph
Abstract
14-3-3 proteins are evolutionarily conserved and ubiquitous proteins that function in a wide variety of biological processes. Here we define a new role for C. elegans 14-3-3 proteins in life span regulation. We identify two C. elegans 14-3-3 proteins as interacting proteins of a major life span regulator, the C. elegans SIR2 ortholog, SIR-2.1. Similar to sir-2.1, we find that overexpression of either 14-3-3 protein (PAR-5 or FTT-2) extends life span and that this is dependent on DAF-16, a forkhead transcription factor (FOXO), another important life span regulator in the insulin/IGF-1 signaling pathway. Furthermore, we show that both 14-3-3 proteins are co-expressed with DAF-16 and SIR-2.1 in the tissues critical for life span regulation. Finally, we show that DAF-16/FOXO also physically interacts with the 14-3-3 proteins. These results suggest that C. elegans 14-3-3 proteins can regulate longevity by cooperating with both SIR-2.1 and DAF-16/FOXO.

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

Temperature °C
20
Lifespan (days)
14.0
Lifespan change (compared to wild type)
-30.00%
Phenotype
ftt-2 RNAi do not significantly shorten the life span of daf-16(mgDf50) animals.
Lifespan comparisons
Double mutant daf-16(mgDf50);ftt-2(RNAi) has a lifespan of 14.0 days, while single mutant ftt-2(RNAi) has a lifespan of 17.0 days, single mutant daf-16(mgDf50) has a lifespan of 14.0 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Dependent
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
20
Diet
OP50
Lifespan (days)
12.8
Lifespan change (compared to wild type)
-32.28%
Phenotype
The ftt-2 gene modulates life span in daf-16 loss-of-function genetic background.
Lifespan comparisons
Double mutant daf-16(mgDf50);ftt-2(RNAi) has a lifespan of 12.8 days, while single mutant ftt-2(RNAi) has a lifespan of 15.6 days, single mutant daf-16(mgDf50) has a lifespan of 13.9 days and wild type has a lifespan of 18.9 days.
Type of interaction
See methods
Almost additive (negative)
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)
7.2
Lifespan change (compared to wild type)
-62.11%
Phenotype
The ftt-2 gene modulates life span in daf-16 loss-of-function genetic background.
Lifespan comparisons
Double mutant daf-16(mgDf50);ftt-2(RNAi) has a lifespan of 7.2 days, while single mutant ftt-2(RNAi) has a lifespan of 14.2 days, single mutant daf-16(mgDf50) has a lifespan of 13.0 days and wild type has a lifespan of 19.0 days.
Type of interaction
See methods
Synergistic (negative)
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-16 ftt-2

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

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-16;ftt-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Ywhaz
Mus musculus	Foxo6;Ywhaq
Mus musculus	Foxo6;Ywhab
Mus musculus	Foxo1;Ywhaz
Mus musculus	Foxo1;Ywhaq
Mus musculus	Foxo1;Ywhab
Mus musculus	Foxo4;Ywhaz
Mus musculus	Foxo4;Ywhaq
Mus musculus	Foxo4;Ywhab
Mus musculus	Foxo3;Ywhaz
Mus musculus	Foxo3;Ywhaq
Mus musculus	Foxo3;Ywhab
Mus musculus	Ywhaz;Foxo6
Mus musculus	Ywhaz;Foxo1
Mus musculus	Ywhaz;Foxo4
Mus musculus	Ywhaz;Foxo3
Mus musculus	Ywhaq;Foxo6
Mus musculus	Ywhaq;Foxo1
Mus musculus	Ywhaq;Foxo4
Mus musculus	Ywhaq;Foxo3
Mus musculus	Ywhab;Foxo6
Mus musculus	Ywhab;Foxo1
Mus musculus	Ywhab;Foxo4
Mus musculus	Ywhab;Foxo3

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 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