glp-1;hcf-1

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Genetic mutants with glp-1, hcf-1 alterations

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

Temperature °C
25
Diet
NGM; OP51
Lifespan (days)
21.4
Lifespan change (compared to wild type)
57.35%
Phenotype
We found that the glp-1(e2141);hcf-1(pk924) double mutant lived much longer than the glp-1(e2141) or hcf-1(pk924) single mutants at 25°C.
Lifespan comparisons
Double mutant glp-1(e2141);hcf-1(pk924) has a lifespan of 21.4 days, while single mutant hcf-1(pk924) has a lifespan of 17.5 days, single mutant glp-1(e2141) has a lifespan of 18.0 days and wild type has a lifespan of 13.6 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Li J et al., 2008, Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS Biol. 6(9):e233 18828672 Click here to select all mutants from this PubMed ID in the graph
Abstract
The transcription factor DAF-16/forkhead box O (FOXO) is a critical longevity determinant in diverse organisms, however the molecular basis of how its transcriptional activity is regulated remains largely unknown. We report that the Caenorhabditis elegans homolog of host cell factor 1 (HCF-1) represents a new longevity modulator and functions as a negative regulator of DAF-16. In C. elegans, hcf-1 inactivation caused a daf-16-dependent lifespan extension of up to 40% and heightened resistance to specific stress stimuli. HCF-1 showed ubiquitous nuclear localization and physically associated with DAF-16. Furthermore, loss of hcf-1 resulted in elevated DAF-16 recruitment to the promoters of its target genes and altered expression of a subset of DAF-16-regulated genes. We propose that HCF-1 modulates C. elegans longevity and stress response by forming a complex with DAF-16 and limiting a fraction of DAF-16 from accessing its target gene promoters, and thereby regulates DAF-16-mediated transcription of selective target genes. As HCF-1 is highly conserved, our findings have important implications for aging and FOXO regulation in mammals.

Search genes: glp-1 hcf-1

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

Entrez ID
Symbol
GenAge
Wormbase ID

177560
hcf-1
View on GenAge (hcf-1)
WBGene00001827

human HCF1 related

Locus: CELE_C46A5.9

Wormbase description: hcf-1 encodes the C. elegans ortholog of human host cell factor (HCF-1), a transcriptional regulator that associates with histone modification enzymes and plays a role in cell cycle progression; in C. elegans, hcf-1 plays a role in regulation of cell division and mitotic histone modification; in addition, HCF-1 functions in determination of adult lifespan as a negative regulator of DAF-16, with which it physically interacts; HCF-1 is a ubiquitously expressed protein that localizes to the nucleus.

Orthologs of glp-1;hcf-1 in SynergyAge

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Species	Gene

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Species	Gene

Orthologs of glp-1 in SynergyAge

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Species	Gene

Orthologs of hcf-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hcf
Mus musculus	Hcfc1