RGD Reference Report - The transcriptional co-activators CREB-binding protein (CBP) and p300 play a critical role in cardiac hypertrophy that is dependent on their histone acetyltransferase activity. - Rat Genome Database

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The transcriptional co-activators CREB-binding protein (CBP) and p300 play a critical role in cardiac hypertrophy that is dependent on their histone acetyltransferase activity.

Authors: Gusterson, RJ  Jazrawi, E  Adcock, IM  Latchman, DS 
Citation: Gusterson RJ, etal., J Biol Chem 2003 Feb 28;278(9):6838-47. Epub 2002 Dec 10.
RGD ID: 1298794
Pubmed: PMID:12477714   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M211762200   (Journal Full-text)

The CBP and p300 proteins are transcriptional co-activators that are involved in a variety of transcriptional pathways in development and in response to specific signaling pathways. We have previously demonstrated that the ability of both these factors to stimulate transcription is greatly enhanced by treatment of cardiac cells with the hypertrophic agent phenylephrine (PE). Here, we show that inhibition of either CBP or p300 with antisense or dominant negative mutant constructs inhibits PE-induced hypertrophy as assayed by atrial naturetic protein production, cardiac cell protein:DNA ratio and cell size. Furthermore, we show that overexpression of CBP or p300 can induce hypertrophy and that this effect requires their histone acetyltransferase (HAT) activity. Moreover, we show that PE can directly enhance CBP HAT activity and that artificial enhancement of HAT activity is sufficient to induce hypertrophy. Hence, CBP and p300 play an essential role in hypertrophy induced by PE, and this effect is mediated via PE-induced enhancement of their HAT activity. This is the first time a role for these factors, and their HAT activity, in hypertrophy has been directly demonstrated.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of protein secretion  IMP 1298794atrial natriuretic proteinRGD 
positive regulation of translation  IMP 1298794increase in protein:DNA ratioRGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
histone acetyltransferase activity  IDA 1298794 RGD 
transcription coactivator activity  TAS 1298794 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiac hypertrophy  IDA 1298794; 1298794 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Crebbp  (CREB binding protein)
Ep300  (E1A binding protein p300)

Objects referenced in this article
Gene CREBBP CREB binding protein Homo sapiens
Gene Crebbp CREB binding protein Mus musculus

Additional Information