Recruitment of p300/CBP in p53-dependent signal pathways
Recruitment of p300/CBP in p53-dependent signal pathways
复制标题
DOI：
10.1016/s0092-8674(00)80304-9
复制
发表时间：
1997-06-27
期刊：
影响因子：
64.5
通讯作者：
Kelly, K
中科院分区：
文献类型：
--
作者：
Avantaggiati, ML;Ogryzko, V;Kelly, K
P53和CBP/p300基因的产物分别与控制细胞生长和调控转录有关。众所周知，P53是基因表达的正负调节因子。在这里，我们证明了野生型和突变型的p53与p300形成了一种特殊的蛋白质复合体。然而，在野生型而不是突变型构象中，p53以p300依赖的方式抑制包含转录因子AP1的DNA结合序列的启动子。P300在P53调节的启动子上刺激P53的转录活性，并增强对P53功能的生理上游调节剂--电离辐射的反应性。P300的显性负性形式阻止了P53的转录激活，并抵消了P53介导的G1停滞和细胞凋亡。这些数据暗示p300是p53信号的重要组成部分，从而为细胞增殖的机制提供了新的见解。
The products of the p53 and CBP/p300 genes have been individually implicated in control of cell growth and regulation of transcription. p53 is known to act as a positive and negative regulator of gene expression. Here we show that p53, in both wild-type and mutant conformation, forms a specific protein complex with p300. However, in its wild-type but not mutant conformation, p53 inhibits a promoter containing the DNA-binding sequences for the transcription factor AP1, in a p300-dependent manner. p300 stimulates the transcriptional activity of p53 on p53-regulated promoters, and it enhances the responsiveness to a physiological upstream modulator of p53 function, ionizing radiation. A dominant negative form of p300 prevents transcriptional activation by p53, and it counteracts p53-mediated G1 arrest and apoptosis. The data implicate p300 as an important component of p53-signaling, thus providing new insight into the mechanisms of cellular proliferation.