TP53 is the most frequently mutated gene in human cancer. Functionally, p53 is activated by a host of stress stimuli and, in turn, governs an exquisitely complex anti-proliferative transcriptional program that touches upon a bewildering array of biological responses. Despite the many unveiled facets of the p53 network, a clear appreciation of how and in what contexts p53 exerts its diverse effects remains unclear. How can we interpret p53's disparate activities and the consequences of its dysfunction to understand how cell type, mutation profile, and epigenetic cell state dictate outcomes, and how might we restore its tumor-suppressive activities in cancer?

中文翻译：

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将 p53 放在上下文中。

TP53是人类癌症中最常发生突变的基因。在功能上，p53 被许多压力刺激激活，反过来，它控制着一个极其复杂的抗增殖转录程序，它涉及一系列令人眼花缭乱的生物反应。尽管 p53 网络有许多公开的方面，但对 p53 如何以及在什么情况下发挥其不同影响的清晰认识仍不清楚。我们如何解释 p53 的不同活性及其功能障碍的后果，以了解细胞类型、突变谱和表观遗传细胞状态如何决定结果，以及我们如何恢复其在癌症中的肿瘤抑制活性？