Espinosa J M, Emerson B M
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Mol Cell. 2001 Jul;8(1):57-69. doi: 10.1016/s1097-2765(01)00283-0.
The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds to two sites at -1.4 and -2.3 kb within the chromatin-assembled p21 promoter and requires the C terminus and the histone acetyltransferase, p300, for transcription. Acetylation of the C terminus by p300 is not necessary for binding or promoter activation. Instead, p300 acetylates p53-bound nucleosomes in the p21 promoter with spreading to the TATA box. Thus, p53 is an active DNA and chromatin binding protein that may selectively regulate its target genes by recruitment of specific cofactors to structurally distinct binding sites.
肿瘤抑制蛋白p53通过调控参与细胞周期阻滞和凋亡的基因，在介导细胞对应激信号的反应中发挥关键作用。除非其C末端被修饰或结构改变，p53被认为对DNA结合无活性。我们发现，未修饰的p53能主动结合染色质组装的p21启动子内-1.4和-2.3 kb处的两个位点，且转录需要C末端和组蛋白乙酰转移酶p300。p300对C末端的乙酰化对于结合或启动子激活并非必需。相反，p300使p21启动子中与p53结合的核小体乙酰化，并扩散至TATA盒。因此，p53是一种活跃的DNA和染色质结合蛋白，它可能通过招募特定辅因子至结构不同的结合位点来选择性调控其靶基因。
