The role of tumor suppressor p53 in the antioxidant defense and metabolism.
The role of tumor suppressor p53 in the antioxidant defense and metabolism.
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DOI：
10.1007/978-94-017-9211-0_18
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发表时间：
2014
影响因子：
--
通讯作者：
Budanov, Andrei V
中科院分区：
文献类型：
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作者：
Budanov, Andrei V
肿瘤抑制因子 p53 在大多数癌症中失活，p53 在抑制癌发生中的关键作用已在许多小鼠模型中得到证实。肿瘤抑制基因 p53 基因的蛋白质产物充当转录调节因子，激活涉及细胞死亡、细胞周期停滞、衰老、DNA 修复和许多其他过程的众多基因的表达。尽管人们为表征 p53 的功能做出了多种努力，但 p53 抑制肿瘤的机制仍然难以捉摸。最近，p53 的新活性如活性氧 (ROS) 和代谢的调节已被描述，并且负责这些功能的 p53 调节基因已被鉴定。代谢紊乱和 ROS 积累是癌发生的特征，这支持了 p53 的许多肿瘤抑制作用可以通过代谢和/或 ROS 调节介导的观点。 p53基因的突变不仅可以使p53的野生型功能失活，还可以赋予p53新的功能，例如激活有助于致癌的新代谢途径。了解 p53 的代谢和抗氧化功能使我们能够开发出在癌症（p53 失活）中恢复 p53 功能的方法，以确保抗癌治疗的最佳结果。
Tumor suppressor p53 is inactivated in most cancers and the critical role of p53 in the suppression of carcinogenesis has been confirmed in many mouse models. The protein product of the tumor suppressor p53 gene works as a transcriptional regulator, activating expression of numerous genes involved in cell death, cell cycle arrest, senescence, DNA-repair and many other processes. In spite of the multiple efforts to characterize the functions of p53, the mechanisms of tumor suppression by p53 are still elusive. Recently, new activities of p53 such as regulation of reactive oxygen species (ROS) and metabolism have been described and the p53-regulated genes responsible for these functions have been identified. Metabolic derangements and accumulation of ROS are features of carcinogenesis, supporting the idea that many tumor suppressive effects of p53 can be mediated by regulation of metabolism and/or ROS. Mutations in the p53 gene can not only inactivate wild type function of p53 but also endow p53 with new functions such as activation of new metabolic pathways contributing to carcinogenesis. Understanding the metabolic and antioxidant functions of p53 allow us to develop approaches to restore p53 function in cancers, where p53 is inactivated, in other to ensure the best outcome of anti-cancer treatment.