Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain
Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain
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DOI：
10.1016/s0092-8674(00)80521-8
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发表时间：
1997-08-22
期刊：
影响因子：
64.5
通讯作者：
Roeder, RG
中科院分区：
文献类型：
--
作者：
Gu, W;Roeder, RG
肿瘤抑制因子p53通过其作为序列特异性DNA结合转录因子的能力发挥抗增殖作用。在这里，我们证明，p53可以通过乙酰化修饰在体内和体外。值得注意的是，p53被其共激活因子p300乙酰化的位点位于已知对p53 DNA结合的调节至关重要的C-末端结构域。此外，乙酰化的p53可以显着刺激其序列特异性DNA结合活性，可能是由于乙酰化诱导的构象变化。这些观察结果清楚地表明了一种新的p53激活途径，重要的是，提供了一个例子，乙酰化介导的功能的非组蛋白调节蛋白的变化。这些结果具有重要意义的分子机制的各种乙酰转移酶的转录辅激活因子，其主要目标已被假定为组蛋白。
The tumor suppressor p53 exerts antiproliferation effects through its ability to function as a sequence-specific DNA-binding transcription factor. Here, we demonstrate that p53 can be modified by acetylation both in vivo and in vitro. Remarkably, the site of p53 that is acetylated by its coactivator, p300, resides in a C-terminal domain known to be critical for the regulation of p53 DNA binding. Furthermore, the acetylation of p53 can dramatically stimulate its sequence-specific DNA-binding activity, possibly as a result of an acetylation-induced conformational change. These observations clearly indicate a novel pathway for p53 activation and, importantly, provide an example of an acetylation-mediated change in the function of a nonhistone regulatory protein. These results have significant implications regarding the molecular mechanisms of various acetyltransferase-containing transcriptional coactivators whose primary targets have been presumed to be histones.