cul-1;glp-1

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Genetic mutants with cul-1, glp-1 alterations

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

Temperature °C
20
Lifespan (days)
22.8
Lifespan change (compared to wild type)
22.58%
Phenotype
Unlike the general proteasomal subunits, RNAi-knockdown of Cullins did not shorten the lifespan of glp-1(e2141ts) mutants or wild-type worms. In fact, some RNAi treatments further extended the glp-1-mutant lifespan. These findings suggest that reducing Cullin function does not generally shorten lifespan, but instead that Cullin complexes might selectively influence the longevity of particular mutants.
Lifespan comparisons
Double mutant cul-1(RNAi);glp-1(e2141ts) has a lifespan of 22.8 days, while single mutant glp-1(e2141ts) has a lifespan of 22.4 days.
Type of interaction
See methods
Synergistic (positive)
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
20
Lifespan (days)
22.6
Lifespan change (compared to wild type)
21.51%
Phenotype
To investigate whether cul-1 was required for lifespan extension by other means, we asked whether cul-1 RNAi shortened the long lifespan of the germ-line-defective glp-1(e2141ts) mutants. We found that it did not
Lifespan comparisons
Double mutant cul-1(RNAi);glp-1(e2141ts) has a lifespan of 22.6 days, while single mutant glp-1(e2141ts) has a lifespan of 24.3 days.
Type of interaction
See methods
Contains dependence
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
20
Lifespan (days)
23.9
Phenotype
To investigate whether cul-1 was required for lifespan extension by other means, we asked whether cul-1 RNAi shortened the long lifespan of the germ-line-defective glp-1(e2141ts) mutants. We found that it did not
Lifespan comparisons
Double mutant cul-1(RNAi);glp-1(e2141ts) has a lifespan of 23.9 days, while single mutant glp-1(e2141ts) has a lifespan of 23.2 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 glp-1

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

176286
glp-1
View on GenAge (glp-1)
WBGene00001609

Protein glp-1

Locus: CELE_F02A9.6

Wormbase description: glp-1 encodes an N-glycosylated transmembrane protein that, along with LIN-12, comprises one of two C. elegans members of the LIN-12/Notch family of receptors; from the N- to the C-terminus, GLP-1 is characterized by ten extracellular EGF-like repeats, three LIN-12/Notch repeats, a CC-linker, a transmembrane domain, a RAM domain, six intracellular ankyrin repeats, and a PEST sequence; in C. elegans, GLP-1 activity is required for cell fate specification in germline and somatic tissues; in the germline, GLP-1, acting as a receptor for the DSL family ligand LAG-2, is essential for mitotic proliferation of germ cells and maintenance of germline stem cells; in somatic tissues, maternally provided GLP-1, acting as a receptor for the DSL family ligand APX-1, is required for inductive interactions that specify the fates of certain embryonic blastomeres; GLP-1 is also required for some later embryonic cell fate decisions, and in these decisions its activity is functionally redundant with that of LIN-12; GLP-1 expression is regulated temporally and spatially via translational control, as GLP-1 mRNA, present ubiquitously in the germline and embryo, yields detectable protein solely in lateral, interior, and endomembranes of distal, mitotic germ cells, and then predominantly in the AB blastomere and its descendants in the early embryo; proper spatial translation of glp-1 mRNA in the embryo is dependent upon genes such as the par genes, that are required for normal anterior-posterior asymmetry in the early embryo; signaling through GLP-1 controls the activity of the downstream Notch pathway components LAG-3 and LAG-1, the latter being predicted to function as part of a transcriptional feedback mechanism that positively regulates GLP-1 expression; signaling through the DNA-binding protein LAG-1 is believed to involve a direct interaction between LAG-1 and the GLP-1 RAM and ankyrin domains

Orthologs of cul-1;glp-1 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 glp-1 in SynergyAge

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Species	Gene