The transcriptional co-activators CBP and p300 are activated via phenylephrine through the p42/p44 MAPK cascade.
The CBP and p300 co-activators play a key role in many aspects of gene regulation being recruited to the DNA via transcription factors that are targets for specific signaling pathways. It has previously been demonstrated that in neuronal cells the ability of CBP and p300 to activate transcription can be directly stimulated by nerve growth factor or calcium-activated signaling pathways. Here we demonstrate that, in cardiac cells, the activity of CBP and p300 is stimulated by phenylephrine (PE) treatment and that they are required for the activation of atrial naturetic factor (ANF) gene expression by PE. Activation of CBP/p300 by PE involves the p42/p44 MAPK pathway and targets primarily the N terminus of p300 and the C terminus of CBP, which are not homologous to one another. To our knowledge, this is the first report of a specific stimulus modulating the activity of CBP and p300 in cardiac cells and it suggests that these factors play an important role in the hypertrophic effect of PE.
Gusterson
Rosalind
R
Institute of Child Health, University College London, 30 Guilford St., London WC1N 1EH, United Kingdom.
Brar
Bhawanjit
B
Faulkes
David
D
Giordano
Antonio
A
Chrivia
John
J
Latchman
David
D
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D050882:CREB-Binding Protein; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D050881:E1A-Associated p300 Protein; D005799:Genes, Dominant; D008156:Luciferases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010656:Phenylephrine / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation
D009687:Nuclear Proteins; D016376:Oligonucleotides, Antisense; D015534:Trans-Activators; D010656:Phenylephrine; D004247:DNA; D008156:Luciferases; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases