cul-1;eat-2

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Genetic mutants with cul-1, eat-2 alterations

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

Temperature °C
25
Lifespan (days)
25.2
Phenotype
We found that cul-1 RNAi had no effect on the lifespan extension of eat-2(ad1116) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);eat-2(ad1116) has a lifespan of 25.2 days, while single mutant eat-2(ad1116) has a lifespan of 27.3 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Temperature °C
25
Lifespan (days)
26.2
Phenotype
We found that cul-1 RNAi had no effect on the lifespan extension of eat-2(ad1116) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);eat-2(ad1116) has a lifespan of 26.2 days, while single mutant eat-2(ad1116) has a lifespan of 26.4 days.
Citation
View abstract
Ghazi A et al., 2007, Regulation of Caenorhabditis elegans lifespan by a proteasomal E3 ligase complex. Proc Natl Acad Sci U S A. 104(14):5947-52 17392428 Click here to select all mutants from this PubMed ID in the graph
Abstract
The proteasome maintains cellular homeostasis by degrading oxidized and damaged proteins, a function known to be impaired during aging. The proteasome also acts in a regulatory capacity through E3 ligases to mediate the spatially and temporally controlled breakdown of specific proteins that impact biological processes. We have identified components of a Skp1-Cul1-F-Box E3 ligase complex that are required for the extended lifespan of Caenorhabditis elegans insulin/insulin-like growth factor-1-signaling (IIS) mutants. The CUL-1 complex functions in postmitotic, adult somatic tissues of IIS mutants to enhance longevity. Reducing IIS function leads to the nuclear accumulation of the DAF-16/FOXO transcription factor, which extends lifespan by regulating downstream longevity genes. These CUL-1 complex genes act, at least in part, by promoting the transcriptional activity of DAF-16/FOXO. Together, our findings describe a role for an important cellular pathway, the proteasomal pathway, in the genetic determination of lifespan.

Search genes: cul-1 eat-2

Entrez ID
Symbol
GenAge
Wormbase ID

176466
cul-1
View on GenAge (cul-1)
WBGene00000836

Cullin-1

Locus: CELE_D2045.6

Wormbase description: cul-1 encodes a cullin, orthologous to Cdc53/Cul1 in S. cerevisiae and CUL-1 in humans (OMIM:603134), that is required both maternally and zygotically for developmentally programmed transitions from the G1 phase of the cell cycle to the GO phase or the apoptotic pathway, and that is probably also required for normally slow G1-to-S phase progression; CUL-1 physically interacts with eight Skp1-related proteins (SKR-1, -2, -3, -4, -7, -8, -9, and -10).

Entrez ID
Symbol
GenAge
Wormbase ID

175072
eat-2
View on GenAge (eat-2)
WBGene00001133

Neuronal acetylcholine receptor subunit eat-2

Locus: CELE_Y48B6A.4

Wormbase description: eat-2 encodes a ligand-gated ion channel subunit most closely related to the non-alpha-subunits of nicotinic acetylcholine receptors (nAChR); EAT-2 functions postsynaptically in pharyngeal muscle to regulate the rate of pharyngeal pumping; eat-2 is also required for normal life span and defecation; a functional EAT-2::GFP fusion protein localizes to two small dots near the junction of pharyngeal muscles pm4 and pm5, which is the site of the posterior-most MC motor neuron processes and the MC synapse; eat-2 genetically interacts with eat-18, which encodes a predicted novel transmembrane protein expressed in pharyngeal muscle and required for proper function of pharyngeal nicotonic receptors.

Orthologs of cul-1;eat-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of cul-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Cul1
Mus musculus	Cul1

Orthologs of eat-2 in SynergyAge

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Species	Gene