Akt-phosphorylation of p300 at Ser-1834 is essential for its histone acetyltransferase and transcriptional activity
Akt-phosphorylation of p300 at Ser-1834 is essential for its histone acetyltransferase and transcriptional activity
复制标题
DOI：
10.1128/mcb.25.15.6592-6602.2005
复制
发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Chen, CC
中科院分区：
文献类型：
--
作者：
Huang, WC;Chen, CC
PI 3 K/Akt通路在许多刺激诱导的基因表达调控中起着关键作用。p300是一种转录辅激活因子，与转录因子协同作用以促进基因表达。在这里，我们表明，Akt被激活，并易位到细胞核中的肿瘤坏死因子α的反应。核Akt与p300结合并在体内和体外磷酸化其Ser-1834。磷酸化诱导p300募集到ICAM-1启动子，导致染色质中组蛋白的乙酰化，并与基础转录机器RNA聚合酶II相关。这两个事件促进ICAM-1基因表达，并被p300 S1834 A突变体、PI 3 K/Akt抑制剂或Akt的小干扰RNA消除。组蛋白乙酰化归因于Akt增强的p300固有组蛋白乙酰转移酶（HAT）活性及其与另一种HAT p/CAF的关联。我们的研究为Akt促进p300转录潜能的分子机制提供了新的见解。
The PI3K/Akt pathway plays a critical role in the regulation of gene expression induced by numerous stimuli. p300, a transcriptional coactivator, acts in concert with transcription factors to facilitate gene expression. Here, we show that Akt is activated and translocated to the nucleus in response to tumor necrosis factor alpha. Nuclear Akt associates with p300 and phosphorylates its Ser-1834 both in vivo and in vitro. The phosphorylation induces recruitment of p300 to the ICAM-1 promoter, leading to the acetylation of histones in chromatin and association with the basal transcriptional machinery RNA polymerase II. These two events facilitate ICAM-1 gene expression and are abolished by the p300 S1834A mutant, inhibitors of PI3K/Akt, or small interfering RNA of Akt. Histone acetylation is attributed to the Akt-enhanced intrinsic histone acetyltransferase (HAT) activity of p300 and its association with another HAT, p/CAF. Our study provides a new insight into the molecular mechanism by which Akt promotes the transcriptional potential of p300.