cul-1;daf-2

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Genetic mutants with cul-1, daf-2 alterations

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

Temperature °C
25
Lifespan (days)
25.1
Phenotype
In multiple experiments, cul-1 RNAi significantly reduced the extended lifespan of daf-2(mu150) mutants as well as daf-2(e1368) and daf-2(e1370) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(e1368) has a lifespan of 25.1 days, while single mutant daf-2(e1368) has a lifespan of 32.7 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)
23.1
Phenotype
To investigate whether cul-1 RNAi might shorten the lifespan of daf-2 mutants by increasing germ-line proliferation (15), we removed the reproductive system by killing the gonad precursor cells Z1 and Z4 with a laser microbeam. cul-1 RNAi still shortened the lifespan of daf-2(e1368) mutants (Fig. 2A and SI Table 3), as well as that of gonad-ablated daf-2(mu150) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(e1368) has a lifespan of 23.1 days, while single mutant daf-2(e1368) has a lifespan of 31.4 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.

Temperature °C
25
Lifespan (days)
24.8
Phenotype
To investigate whether cul-1 RNAi might shorten the lifespan of daf-2 mutants by increasing germ-line proliferation (15), we removed the reproductive system by killing the gonad precursor cells Z1 and Z4 with a laser microbeam. cul-1 RNAi still shortened the lifespan of daf-2(e1368) mutants (Fig. 2A and SI Table 3), as well as that of gonad-ablated daf-2(mu150) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(e1368) has a lifespan of 24.8 days, while single mutant daf-2(e1368) has a lifespan of 30.5 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)
26.7
Phenotype
To investigate whether cul-1 RNAi might shorten the lifespan of daf-2 mutants by increasing germ-line proliferation (15), we removed the reproductive system by killing the gonad precursor cells Z1 and Z4 with a laser microbeam. cul-1 RNAi still shortened the lifespan of daf-2(e1368) mutants (Fig. 2A and SI Table 3), as well as that of gonad-ablated daf-2(mu150) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(e1368) has a lifespan of 26.7 days, while single mutant daf-2(e1368) has a lifespan of 39.1 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.

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

Temperature °C
25
Lifespan (days)
31.1
Phenotype
In multiple experiments, cul-1 RNAi significantly reduced the extended lifespan of daf-2(mu150) mutants as well as daf-2(e1368) and daf-2(e1370) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(e1370) has a lifespan of 31.1 days, while single mutant daf-2(e1370) has a lifespan of 40.8 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)
32.8
Phenotype
In multiple experiments, cul-1 RNAi significantly reduced the extended lifespan of daf-2(mu150) mutants as well as daf-2(e1368) and daf-2(e1370) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(e1370) has a lifespan of 32.8 days, while single mutant daf-2(e1370) has a lifespan of 54.8 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.

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

Temperature °C
25
Lifespan (days)
21.5
Lifespan change (compared to wild type)
15.59%
Phenotype
Inactivating regulatory proteasomal function by RNAi-knockdown of the six predicted worm Cullins, CUL-1 to -6 , had distinct effects on the extended lifespan of daf-2(mu150) mutants. Some knockdowns suppressed lifespan extension (cul-1, cul-3), some had less significant effects (cul-4), and others had no effect at all (cul-5)
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(mu150) has a lifespan of 21.5 days, while single mutant daf-2(mu150) has a lifespan of 28.8 days.
Type of interaction
See methods
Dependent
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)
25.2
Phenotype
In multiple experiments, cul-1 RNAi significantly reduced the extended lifespan of daf-2(mu150) mutants as well as daf-2(e1368) and daf-2(e1370) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(mu150) has a lifespan of 25.2 days, while single mutant daf-2(mu150) has a lifespan of 33.4 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.

Temperature °C
25
Lifespan (days)
25.0
Phenotype
In multiple experiments, cul-1 RNAi significantly reduced the extended lifespan of daf-2(mu150) mutants as well as daf-2(e1368) and daf-2(e1370) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(mu150) has a lifespan of 25 days, while single mutant daf-2(mu150) has a lifespan of 32.3 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)
30.8
Phenotype
In multiple experiments, cul-1 RNAi significantly reduced the extended lifespan of daf-2(mu150) mutants as well as daf-2(e1368) and daf-2(e1370) mutants
Lifespan comparisons
Double mutant cul-1(RNAi);daf-2(mu150) has a lifespan of 30.8 days, while single mutant daf-2(mu150) has a lifespan of 37.8 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 daf-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

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.

Orthologs of cul-1;daf-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Cul1;InR
Mus musculus	Cul1;Insr
Mus musculus	Cul1;Igf1r
Mus musculus	Cul1;Insrr

Orthologs of cul-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Cul1
Mus musculus	Cul1

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