The extent to which transcription factors read and respond to specific information content within short DNA sequences remains an important question that the tumor suppressor p53 is helping us answer. We discuss recent insights into how local information content at p53 binding sites might control modes of p53 target gene activation and cell fate decisions. Significant prior work has yielded data supporting two potential models of how p53 determines cell fate through its target genes: a selective target gene binding and activation model and a p53 level threshold model. Both of these models largely revolve around an analogy of whether p53 is acting in a “smart” or “dumb” manner. Here, we synthesize recent and past studies on p53 decoding of DNA sequence, chromatin context, and cellular signaling cascades to elicit variable cell fates critical in human development, homeostasis, and disease.

转录因子在多大程度上读取和响应短 DNA 序列中的特定信息内容仍然是肿瘤抑制因子 p53 正在帮助我们回答的一个重要问题。我们讨论了 p53 结合位点的局部信息内容如何控制 p53 靶基因激活和细胞命运决定的模式的最新见解。先前的重要工作已经获得了支持 p53 如何通过其靶基因决定细胞命运的两种潜在模型的数据：选择性靶基因结合和激活模型以及 p53 水平阈值模型。这两个模型很大程度上都围绕 p53 是否以“聪明”或“愚蠢”的方式发挥作用进行类比。在这里，我们综合了最近和过去关于 p53 解码 DNA 序列、染色质背景和细胞信号级联的研究，以引发对人类发育、体内平衡和疾病至关重要的可变细胞命运。