Gu W, Roeder R G
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York 10021, USA.
Cell. 1997 Aug 22;90(4):595-606. doi: 10.1016/s0092-8674(00)80521-8.
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.
肿瘤抑制因子p53通过其作为序列特异性DNA结合转录因子的功能发挥抗增殖作用。在此，我们证明p53在体内和体外均可被乙酰化修饰。值得注意的是，其共激活因子p300使p53发生乙酰化的位点位于一个对p53 DNA结合调控至关重要的C末端结构域。此外，p53的乙酰化可显著刺激其序列特异性DNA结合活性，这可能是乙酰化诱导的构象变化所致。这些观察结果清楚地表明了一条p53激活的新途径，重要的是，提供了一个非组蛋白调节蛋白功能通过乙酰化介导改变的例子。这些结果对于各种主要靶标被认为是组蛋白的含乙酰转移酶转录共激活因子的分子机制具有重要意义。
