daf-16;rle-1

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Genetic mutants with daf-16, rle-1 alterations

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

Temperature °C
25
Lifespan (days)
22.7
Lifespan change (compared to wild type)
18.85%
Phenotype
Removing one copy of the daf-16 gene, in rle-1-/-;daf-16+/- animals, partially suppressed the rle-1-/- mutant lifespan extension. However, when compared to N2 (or daf-16+/-) animals, rle-1-/-;daf-16+/- worms still live slightly longer, suggesting that other protein(s) involved in C. elegans aging may also be regulated by RLE-1. Taken together, our results indicate that RLE-1 regulates C. elegans aging in a DAF-16-dependent manner.
Lifespan comparisons
Double mutant daf-16(KD);rle-1(cxTi510) has a lifespan of 22.7 days, while single mutant rle-1(cxTi510) has a lifespan of 23.9 days, single mutant daf-16(KD) has a lifespan of 19.1 days and wild type has a lifespan of 19.1 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Li W et al., 2007, RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. Dev Cell. 12(2):235-46 17276341 Click here to select all mutants from this PubMed ID in the graph
Abstract
The forkhead transcription factor, DAF-16, a downstream target of the insulin/IGF-I signaling pathway in C. elegans, is indispensable both for lifespan regulation and stress resistance. The molecular mechanisms involved in regulating DAF-16 transcriptional activation remain undefined. Here, we have identified an E3 ubiquitin ligase, RLE-1 (regulation of longevity by E3), which regulates aging in C. elegans. Disruption of RLE-1 expression in C. elegans increases lifespan; this extension of lifespan is due to elevated DAF-16 protein but not to changes of daf-16 mRNA levels. We have also found that RLE-1 catalyzes DAF-16 ubiquitination, leading to degradation by the proteasome. Elimination of RLE-1 expression in C. elegans causes increased transcriptional activation and sustained nuclear localization of DAF-16. Overexpression of DAF-16 in rle-1 mutants increases worm lifespan, while disruption of DAF-16 expression in rle-1 mutants reverses their longevity. Thus, RLE-1 is an E3 ubiquitin ligase of DAF-16 that regulates C. elegans aging.

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

Temperature °C
25
Lifespan (days)
25.4
Lifespan change (compared to wild type)
32.98%
Phenotype
When RLE-1 expression was disrupted in daf-16::gfp animals by crossing rle-1 mutants into the daf-16::gfp background, the lifespan of daf-16::gfp increased an additional 10%. These results indicate that disruption of RLE-1 adds to the overexpression of DAF-16 to further extends C. elegans lifespan.
Lifespan comparisons
Double mutant daf-16(OE);rle-1(cxTi510) has a lifespan of 25.4 days, while single mutant rle-1(cxTi510) has a lifespan of 23.9 days, single mutant daf-16(OE) has a lifespan of 23.1 days and wild type has a lifespan of 19.1 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Li W et al., 2007, RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. Dev Cell. 12(2):235-46 17276341 Click here to select all mutants from this PubMed ID in the graph
Abstract
The forkhead transcription factor, DAF-16, a downstream target of the insulin/IGF-I signaling pathway in C. elegans, is indispensable both for lifespan regulation and stress resistance. The molecular mechanisms involved in regulating DAF-16 transcriptional activation remain undefined. Here, we have identified an E3 ubiquitin ligase, RLE-1 (regulation of longevity by E3), which regulates aging in C. elegans. Disruption of RLE-1 expression in C. elegans increases lifespan; this extension of lifespan is due to elevated DAF-16 protein but not to changes of daf-16 mRNA levels. We have also found that RLE-1 catalyzes DAF-16 ubiquitination, leading to degradation by the proteasome. Elimination of RLE-1 expression in C. elegans causes increased transcriptional activation and sustained nuclear localization of DAF-16. Overexpression of DAF-16 in rle-1 mutants increases worm lifespan, while disruption of DAF-16 expression in rle-1 mutants reverses their longevity. Thus, RLE-1 is an E3 ubiquitin ligase of DAF-16 that regulates C. elegans aging.

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

Temperature °C
25
Lifespan (days)
15.7
Lifespan change (compared to wild type)
-17.80%
Phenotype
Disruption of DAF-16 expression in rle-1 mutants reduced their longevity, indicating that RLE-1 strictly depends on DAF-16 to regulate C. elegans lifespan
Lifespan comparisons
Double mutant daf-16(mu86);rle-1(cxTi510) has a lifespan of 15.7 days, while single mutant rle-1(cxTi510) has a lifespan of 23.9 days, single mutant daf-16(mu86) has a lifespan of 14.3 days and wild type has a lifespan of 19.1 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Li W et al., 2007, RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination. Dev Cell. 12(2):235-46 17276341 Click here to select all mutants from this PubMed ID in the graph
Abstract
The forkhead transcription factor, DAF-16, a downstream target of the insulin/IGF-I signaling pathway in C. elegans, is indispensable both for lifespan regulation and stress resistance. The molecular mechanisms involved in regulating DAF-16 transcriptional activation remain undefined. Here, we have identified an E3 ubiquitin ligase, RLE-1 (regulation of longevity by E3), which regulates aging in C. elegans. Disruption of RLE-1 expression in C. elegans increases lifespan; this extension of lifespan is due to elevated DAF-16 protein but not to changes of daf-16 mRNA levels. We have also found that RLE-1 catalyzes DAF-16 ubiquitination, leading to degradation by the proteasome. Elimination of RLE-1 expression in C. elegans causes increased transcriptional activation and sustained nuclear localization of DAF-16. Overexpression of DAF-16 in rle-1 mutants increases worm lifespan, while disruption of DAF-16 expression in rle-1 mutants reverses their longevity. Thus, RLE-1 is an E3 ubiquitin ligase of DAF-16 that regulates C. elegans aging.

Search genes: daf-16 rle-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.

Entrez ID
Symbol
GenAge
Wormbase ID

176525
rle-1
View on GenAge (rle-1)
WBGene00010923

Regulation of longevity by E3 ubiquitin-protein ligase

Locus: CELE_M142.6

Wormbase description: none available

Orthologs of daf-16;rle-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Rc3h2
Mus musculus	Foxo6;Rc3h1
Mus musculus	Foxo1;Rc3h2
Mus musculus	Foxo1;Rc3h1
Mus musculus	Foxo4;Rc3h2
Mus musculus	Foxo4;Rc3h1
Mus musculus	Foxo3;Rc3h2
Mus musculus	Foxo3;Rc3h1
Mus musculus	Rc3h2;Foxo6
Mus musculus	Rc3h2;Foxo1
Mus musculus	Rc3h2;Foxo4
Mus musculus	Rc3h2;Foxo3
Mus musculus	Rc3h1;Foxo6
Mus musculus	Rc3h1;Foxo1
Mus musculus	Rc3h1;Foxo4
Mus musculus	Rc3h1;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 rle-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Rc3h2
Mus musculus	Rc3h1