PDF(Pubmed)
Abstract：
p53 was discovered 45 years ago as an SV40 large T antigen binding protein, coded by the most frequently mutated TP53 gene in human cancers. As a transcription factor, p53 is tightly regulated by a rich network of post-translational modifications to execute its diverse functions in tumor suppression. Although early studies established p53-mediated cell-cycle arrest, apoptosis, and senescence as the classic barriers in cancer development, a growing number of new functions of p53 have been discovered and the scope of p53-mediated anti-tumor activity is largely expanded. Here, we review the complexity of different layers of p53 regulation, and the recent advance of the p53 pathway in metabolism, ferroptosis, immunity, and others that contribute to tumor suppression. We also discuss the challenge regarding how to activate p53 function specifically effective in inhibiting tumor growth without harming normal homeostasis for cancer therapy.
摘要：
p53是45年前发现的SV40大T抗原结合蛋白，由人类癌症中最常见的突变TP53基因编码。作为转录因子,p53受到丰富的翻译后修饰网络的严格调节，以执行其在肿瘤抑制中的多种功能。尽管早期研究建立了p53介导的细胞周期阻滞，凋亡，衰老是癌症发展的经典障碍，越来越多的p53新功能被发现，p53介导的抗肿瘤活性的范围大大扩大。这里,我们回顾了p53调控的不同层次的复杂性，以及代谢中p53通路的最新进展，铁性凋亡,豁免权,和其他有助于肿瘤抑制的。我们还讨论了如何激活p53功能，特别有效地抑制肿瘤生长而不损害癌症治疗的正常稳态的挑战。
