cbp-1;glp-1

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Genetic mutants with cbp-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)
17.94
Lifespan change (compared to wild type)
-4.98%
Phenotype
Cbp-1 RNAi blocks life extension by DR produced by three protocols. cbp-1 RNAi does not affect egg laying in N2 worms.
Lifespan comparisons
Double mutant cbp-1(RNAi);glp-1(e2141) has a lifespan of 17.94 days, while single mutant cbp-1(RNAi) has a lifespan of 15.5 days, single mutant glp-1(e2141) has a lifespan of 23.29 days and wild type has a lifespan of 18.88 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Zhang M et al., 2009, Role of CBP and SATB-1 in aging, dietary restriction, and insulin-like signaling. PLoS Biol. 7(11):e1000245 19924292 Click here to select all mutants from this PubMed ID in the graph
Abstract
How dietary restriction (DR) increases lifespan and decreases disease burden are questions of major interest in biomedical research. Here we report that hypothalamic expression of CREB-binding protein (CBP) and CBP-binding partner Special AT-rich sequence binding protein 1 (SATB-1) is highly correlated with lifespan across five strains of mice, and expression of these genes decreases with age and diabetes in mice. Furthermore, in Caenorhabditis elegans, cbp-1 is induced by bacterial dilution DR (bDR) and the daf-2 mutation, and cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR, partially blocks lifespan extension by the daf-2 mutation but not of cold, and blocks delay of other age-related pathologies by bDR. Inhibiting the C. elegans ortholog of SATB-1 and CBP-binding partners daf-16 and hsf-1 also attenuates lifespan extension by bDR, but not other protocols of DR. In a transgenic Abeta42 model of Alzheimer's disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Abeta42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Abeta42-related pathology, protective effects completely blocked by cbp-1 RNAi. Other factors implicated in lifespan extension are also CBP-binding partners, suggesting that CBP constitutes a common factor in the modulation of lifespan and disease burden by DR and the insulin/IGF1 signaling pathway.

Search genes: cbp-1 glp-1

Entrez ID
Symbol
GenAge
Wormbase ID

176380
cbp-1
View on GenAge (cbp-1)
WBGene00000366

Protein cbp-1

Locus: CELE_R10E11.1

Wormbase description: cbp-1 encodes a homolog of the mammalian transcriptional cofactors CBP (OMIM:600140) and p300 (E1A-BINDING PROTEIN, 300-KD; OMIM:602700) that have been shown to possess histone acetyltransferase activity, and which, when mutated, lead to Rubinstein-Taybi syndrome (OMIM:180849) and colorectal cancer (OMIM:114500); at least one splicing form of CBP-1 exhibits histone acetyltransferase (HAT) activity in vitro and has a glutamine/asparagine-rich domain; CBP-1 is required during embryogenesis for differentiation of all non-neuronal somatic cell types; CBP-1 is expressed very early in embryogenesis, suggesting that it may interact with maternally provided transcription factors, such as SKN-1, to specific developmental fates.

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 cbp-1;glp-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of cbp-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	nej
Mus musculus	Ep300

Orthologs of glp-1 in SynergyAge

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Species	Gene