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Symbol: cbp-1 Name: CBP/p300 homolog 1 Entrez gene ID: 176380 Ensembl gene ID: R10E11.1 Species: Worm (Taxid: 6239) Functional description: Protein CBP-1; Protein cbp-1 [Source:UniProtKB/Swiss-Prot;Acc:P34545] [Ensembl]; 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. Two protein products of this gene are predicted to contain a glutamine/asparagine (Q/N)-rich ('prion') domain, by the algorithm of Michelitsch and Weissman (as of the WS77 release of WormBase, i.e., in wormpep77). Proteins bearing such domains can sometimes stably exist in at least two distinct physical states, each associated with a different phenotype; propagation of one of these traits is achieved by a self-perpetuating change in the protein from one form to the other, mediated by conformational changes in the glutamine/asparagine-rich domain. Prion domains are both modular and transferable to other proteins, on which they can confer a heritable epigenetic alteration of function; existing bioinformatics data indicate that they are rare in non-eukarya, but common in eukarya. Therefore, it is possible that this gene's protein product undergoes epigenetic control of protein activity, through heritable epigenetic modulation of protein function by self-perpetuating conformational conversions of normal proteins in healthy cells. It is important to note that this is distinct from, though mechanistically analogous to, disease states associated with prion propagation and amyloidogenesis. [WormBase] Observation: bDR and daf-2 mutation induce cbp-1 expression. There is no decrease in cbp-1 expression in whole C. elegans during aging. Overexpression of cbp-1 does not significantly affect lifespan. daf-16 RNAi and cbp-1 RNAi reduce average lifespan under AL to about the same extent. Inhibiting cbp-1 via RNAi by 50%, specifically in adult phase and completely blocks lifespan extension of DD, bDR as well as eat-2, glp-1 and clk-1 mutation, but only partially that of daf-2 mutation and not at all that of cold. cbp-1 RNAi completely blocks the lifespan increase by daf-2 mutation under bDR. cbp-1 RNAi blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi prevents protective effects of bDR and accelerates ABeta42-related pathology. bDR significantly delays onset of paralysis even in presence of cbp-1 RNAi. cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR (mutation of eat-2), partly by daf-2 mutation but not of cold and blocks the delay of other age-related pathologies by bDR. cbp-1 RNAi has no effect on lifespan in daf-16 hypomorphic mutants. Combining cbp-1 and daf-16 RNAi in wild-type produces similar lifespan as either alone. Resistance to oxidative stress is strikingly reduced by cbp-1 RNAi and cbp-1 RNAi attenuates the protection against oxidative stress by bDR. cbp-1 RNAi accelerates accumulation of autofluorescence, but has no effect on activity, egg laying, or pharyngeal pumping. cbp-1 RNAi does not block induction of daf-16 or hsf-1 by bDR, but does block the induction of DAF-16 target gene, sod-3, and HSF-1 target gene, sip-1 by bDR. cbp-1 RNAi blocks induction of sod-3 expression by daf-2 RNAi. cbp-1 RNAi does not block the increased Nile Red staining produced by daf-2 mutation, but enhanced Nile Red staining. cbp-1 RNAi blocks the effect of bDR on metabolic gene expression from glycolysis towards beta-oxidation. Drugs that enhance histone acetylation increase lifespan and reduce ABeta42-related pathologies, but these protective effects are completely blocked by cbp-1 RNAi. cbp-1 RNAi decreases H4 Lys 5 acetylation and blocks the extension of lifespan as well as delays the onset of paralysis by ABeta1-42 transgene under AL and bDR by sodium butyrate (NaB) and trichostatin (TSA). cbp-1 RNAi does produce dye-filling defects in all C. elegans amphid neurons (ASI, ADL, ASK, AWB, ASH, and ASJ) [19924292]. Interventions: Assays: Organismal Lifespan Classification: Aging Relevance Analysis/Source:  GenAge GenDRHomologs Orthologs Edit \ Update (Admin) | Delete |
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