The transcriptional co-activators CBP and p300 are activated via phenylephrine through the p42/p44 MAPK cascade
The transcriptional co-activators CBP and p300 are activated via phenylephrine through the p42/p44 MAPK cascade
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DOI：
10.1074/jbc.m104626200
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发表时间：
2002-01-25
影响因子：
4.8
通讯作者：
Latchman, D
中科院分区：
文献类型：
--
作者：
Gusterson, R;Brar, B;Latchman, D
CBP和p300共激活因子在基因调控的许多方面发挥关键作用，通过转录因子被招募到DNA中，这些转录因子是特定信号传导途径的靶点。以前已经证明，在神经元细胞中，CBP和p300激活转录的能力可以直接由神经生长因子或钙激活的信号通路刺激。在这里，我们证明，在心脏细胞中，CBP和p300的活性刺激苯肾上腺素（PE）治疗，他们所需的激活心房利钠因子（ANF）基因表达的PE。PE对CBP/p300的激活涉及p42/p44 MAPK途径，主要靶向p300的N末端和CBP的C末端，这两个位点彼此不同源。据我们所知，这是第一个报告的一个特定的刺激调节CBP和p300在心肌细胞中的活性，这表明这些因素在PE的肥大效应中发挥重要作用。
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.