ftt-2;hcf-1

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Genetic mutants with ftt-2, hcf-1 alterations

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

Temperature °C
25
Diet
NGM; HT115
Lifespan (days)
12.4
Lifespan change (compared to wild type)
-33.33%
Phenotype
Knocking down of ftt-2 alone did not substantially reduce hcf-1(pk924) lifespan.
Lifespan comparisons
Double mutant ftt-2(RNAi);hcf-1(pk924) has a lifespan of 12.4 days, while single mutant ftt-2(RNAi) has a lifespan of 14.0 days, single mutant hcf-1(pk924) has a lifespan of 22.5 days and wild type has a lifespan of 18.6 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
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)
15.6
Lifespan change (compared to wild type)
-7.14%
Phenotype
Knocking down of ftt-2 alone did not substantially reduce hcf-1(pk924) lifespan.
Lifespan comparisons
Double mutant ftt-2(RNAi);hcf-1(pk924) has a lifespan of 15.6 days, while single mutant ftt-2(RNAi) has a lifespan of 16.1 days, single mutant hcf-1(pk924) has a lifespan of 18.1 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.

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

Temperature °C
25
Diet
NGM; OP50
Lifespan (days)
18.9
Lifespan change (compared to wild type)
19.62%
Phenotype
A null mutation of ftt-2(n4426) was only able to slightly decrease the lifespan of hcf-1 mutants.
Lifespan comparisons
Double mutant ftt-2(n4426);hcf-1(pk924) has a lifespan of 18.9 days, while single mutant ftt-2(n4426) has a lifespan of 12.6 days, single mutant hcf-1(pk924) has a lifespan of 22.2 days and wild type has a lifespan of 15.8 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; OP50
Lifespan (days)
19.2
Lifespan change (compared to wild type)
21.52%
Phenotype
A null mutation of ftt-2(n4426) was only able to slightly decrease the lifespan of hcf-1 mutants.
Lifespan comparisons
Double mutant ftt-2(n4426);hcf-1(pk924) has a lifespan of 19.2 days, while single mutant ftt-2(n4426) has a lifespan of 12.6 days, single mutant hcf-1(pk924) has a lifespan of 22.2 days and wild type has a lifespan of 15.8 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; OP50
Lifespan (days)
18.8
Lifespan change (compared to wild type)
24.50%
Phenotype
A null mutation of ftt-2(n4426) was only able to slightly decrease the lifespan of hcf-1 mutants.
Lifespan comparisons
Double mutant ftt-2(n4426);hcf-1(pk924) has a lifespan of 18.8 days, while single mutant ftt-2(n4426) has a lifespan of 14.2 days, single mutant hcf-1(pk924) has a lifespan of 19.8 days and wild type has a lifespan of 15.1 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; OP50
Lifespan (days)
19.4
Lifespan change (compared to wild type)
28.48%
Phenotype
A null mutation of ftt-2(n4426) was only able to slightly decrease the lifespan of hcf-1 mutants.
Lifespan comparisons
Double mutant ftt-2(n4426);hcf-1(pk924) has a lifespan of 19.4 days, while single mutant ftt-2(n4426) has a lifespan of 14.2 days, single mutant hcf-1(pk924) has a lifespan of 19.8 days and wild type has a lifespan of 15.1 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; OP50
Lifespan (days)
19.1
Lifespan change (compared to wild type)
23.23%
Phenotype
A null mutation of ftt-2(n4426) was only able to slightly decrease the lifespan of hcf-1 mutants.
Lifespan comparisons
Double mutant ftt-2(n4426);hcf-1(pk924) has a lifespan of 19.1 days, while single mutant ftt-2(n4426) has a lifespan of 13.4 days, single mutant hcf-1(pk924) has a lifespan of 21.0 days and wild type has a lifespan of 15.5 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.

Search genes: ftt-2 hcf-1

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.

Entrez ID
Symbol
GenAge
Wormbase ID

177560
hcf-1
View on GenAge (hcf-1)
WBGene00001827

human HCF1 related

Locus: CELE_C46A5.9

Wormbase description: hcf-1 encodes the C. elegans ortholog of human host cell factor (HCF-1), a transcriptional regulator that associates with histone modification enzymes and plays a role in cell cycle progression; in C. elegans, hcf-1 plays a role in regulation of cell division and mitotic histone modification; in addition, HCF-1 functions in determination of adult lifespan as a negative regulator of DAF-16, with which it physically interacts; HCF-1 is a ubiquitously expressed protein that localizes to the nucleus.

Orthologs of ftt-2;hcf-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	14-3-3zeta;Hcf
Mus musculus	Hcfc1;Ywhaz
Mus musculus	Hcfc1;Ywhaq
Mus musculus	Hcfc1;Ywhab
Mus musculus	Hcf;14-3-3zeta

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

Orthologs of hcf-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hcf
Mus musculus	Hcfc1