Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
Int J Mol Sci. 2019 Nov 9;20(22):5605. doi: 10.3390/ijms20225605.
The tumor suppressor functions of p53 and its roles in regulating the cell cycle, apoptosis, senescence, and metabolism are accomplished mainly by its interactions with DNA. p53 works as a transcription factor for a significant number of genes. Most p53 target genes contain so-called p53 response elements in their promoters, consisting of 20 bp long canonical consensus sequences. Compared to other transcription factors, which usually bind to one concrete and clearly defined DNA target, the p53 consensus sequence is not strict, but contains two repeats of a 5'RRRCWWGYYY3' sequence; therefore it varies remarkably among target genes. Moreover, p53 binds also to DNA fragments that at least partially and often completely lack this consensus sequence. p53 also binds with high affinity to a variety of non-B DNA structures including Holliday junctions, cruciform structures, quadruplex DNA, triplex DNA, DNA loops, bulged DNA, and hemicatenane DNA. In this review, we summarize information of the interactions of p53 with various DNA targets and discuss the functional consequences of the rich world of p53 DNA binding targets for its complex regulatory functions.
p53 的抑瘤功能及其在调节细胞周期、细胞凋亡、衰老和代谢中的作用主要通过与 DNA 的相互作用来实现。p53 作为许多基因的转录因子发挥作用。大多数 p53 靶基因的启动子中含有所谓的 p53 反应元件,由 20 个碱基长的典型共识序列组成。与通常结合一个具体和明确的 DNA 靶标的其他转录因子相比,p53 共识序列并不严格,但包含两个 5'RRRCWWGYYY3'序列的重复;因此,它在靶基因之间差异显著。此外,p53 还结合至少部分且通常完全缺乏此共识序列的 DNA 片段。p53 还与多种非 B DNA 结构具有高亲和力,包括 Holliday 连接、十字形结构、四链 DNA、三链 DNA、DNA 环、膨出 DNA 和半夹合 DNA。在这篇综述中,我们总结了 p53 与各种 DNA 靶标的相互作用信息,并讨论了 p53 DNA 结合靶标丰富多样的世界对其复杂调节功能的功能后果。