cul-4;glp-1

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Genetic mutants with cul-4, glp-1 alterations

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

Temperature °C
20
Lifespan (days)
24.6
Lifespan change (compared to wild type)
32.26%
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-4(RNAi);glp-1(e2141ts) has a lifespan of 24.6 days, while single mutant glp-1(e2141ts) has a lifespan of 22.4 days, single mutant cul-4(RNAi) has a lifespan of 19.7 days and wild type has a lifespan of 18.6 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.

Search genes: cul-4 glp-1

Entrez ID
Symbol
GenAge
Wormbase ID

174198
cul-4
View on GenAge (cul-4)
WBGene00000839

Cullin-4

Locus: CELE_F45E12.3

Wormbase description: cul-4 encodes one of six C. elegans cullin proteins; CUL-4 activity is essential for negative regulation of DNA-replication licensing and thus, for maintenance of genome stability; in regulating DNA replication, CUL-4 functions as part of a CUL-4/DDB-1 ubiquitin ligase complex that degrades the replication licensing factor CDT-1 and indirectly promotes nuclear export of the replication licensing factor CDC-6 by negatively regulating the levels of the CKI-1 CDK inhibitor; cul-4 mRNA is expressed throughout development with highest levels seen in embryos and lower levels seen in larvae and adults; maternal cul-4 mRNA is present in early embryos and larval and adult mRNA is most notably present in the intestine and germ line.

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-4;glp-1 in SynergyAge

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Orthologs of cul-4 in SynergyAge

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Orthologs of glp-1 in SynergyAge

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