The p53 Pathway and Metabolism: The Tree That Hides the Forest.
The p53 Pathway and Metabolism: The Tree That Hides the Forest.
复制标题
DOI：
10.3390/cancers13010133
复制
发表时间：
2021-01-04
期刊：
影响因子：
5.2
通讯作者：
Le Cam L
中科院分区：
文献类型：
--
作者：
Lahalle A;Lacroix M;De Blasio C;Cissé MY;Linares LK;Le Cam L
p53 途径是一种主要的肿瘤抑制途径，通过调节 DNA 修复、细胞周期进程、细胞死亡或衰老来防止异常细胞的增殖。 p53 调节的多种细胞过程最近扩展到代谢的控制，许多研究支持 p53 相关代谢活动的扰动与癌症发展相关的观点。一系列证据支持这样的观点：除了 p53 之外，该分子级联的其他关键成分也是代谢的重要调节因子。在这里，我们阐述了 p53 通路控制的代谢网络被低估的复杂性，并展示了它的扰动如何导致人类疾病，包括癌症、衰老和代谢疾病。 p53 通路在大多数（如果不是全部）人类癌症中功能失活。 p53 蛋白是众多应激相关分子级联反应的核心效应子。 p53 控制着一种保护机制，通过调节 DNA 修复、细胞周期进程、细胞死亡或衰老来防止异常细胞的积累及其转化。 p53 调节的多种细胞过程最近扩展到代谢的控制，许多研究支持这样的观点，即 p53 相关代谢活动的扰动与癌症的发展以及其他病理生理状况（包括衰老、II 型糖尿病和肝病）有关。尽管比 p53 代谢活动的记录要少得多，但汇聚的证据表明，该肿瘤抑制途径的其他关键成分也通过 p53 依赖性和 p53 独立机制参与细胞代谢。因此，至少从代谢的角度来看，p53途径必须被视为非线性途径，但这些p53调节剂控制的复杂代谢网络以及它们的活动与p53代谢功能协调的机制仍然知之甚少。在这篇综述中，我们重点介绍了由 p53 途径的几个核心成分控制的一些代谢途径及其在组织稳态、代谢疾病和癌症中的作用。
The p53 pathway is a major tumor suppressor pathway that prevents the propagation of abnormal cells by regulating DNA repair, cell cycle progression, cell death, or senescence. The multiple cellular processes regulated by p53 were more recently extended to the control of metabolism, and many studies support the notion that perturbations of p53-associated metabolic activities are linked to cancer development. Converging lines of evidence support the notion that, in addition to p53, other key components of this molecular cascade are also important regulators of metabolism. Here, we illustrate the underestimated complexity of the metabolic network controlled by the p53 pathway and show how its perturbation contributes to human diseases including cancer, aging, and metabolic diseases. The p53 pathway is functionally inactivated in most, if not all, human cancers. The p53 protein is a central effector of numerous stress-related molecular cascades. p53 controls a safeguard mechanism that prevents accumulation of abnormal cells and their transformation by regulating DNA repair, cell cycle progression, cell death, or senescence. The multiple cellular processes regulated by p53 were more recently extended to the control of metabolism and many studies support the notion that perturbations of p53-associated metabolic activities are linked to cancer development, as well as to other pathophysiological conditions including aging, type II diabetes, and liver disease. Although much less documented than p53 metabolic activities, converging lines of evidence indicate that other key components of this tumor suppressor pathway are also involved in cellular metabolism through p53-dependent as well as p53-independent mechanisms. Thus, at least from a metabolic standpoint, the p53 pathway must be considered as a non-linear pathway, but the complex metabolic network controlled by these p53 regulators and the mechanisms by which their activities are coordinated with p53 metabolic functions remain poorly understood. In this review, we highlight some of the metabolic pathways controlled by several central components of the p53 pathway and their role in tissue homeostasis, metabolic diseases, and cancer.
登录
查看更多内容
影响因子：
4.6
作者：
Funauchi Y;Tanikawa C;Yi Lo PH;Mori J;Daigo Y;Takano A;Miyagi Y;Okawa A;Nakamura Y;Matsuda K
通讯作者：
Matsuda K
影响因子：
17.1
作者：
Cisse, Madi Y.;Pyrdziak, Samuel;Linares, Laetitia K.
通讯作者：
Linares, Laetitia K.
影响因子：
8.8
作者：
Grote, David;Moison, Celine;Sauvageau, Guy
通讯作者：
Sauvageau, Guy
影响因子：
64.5
作者：
Bond, GL;Hu, WW;Levine, AJ
通讯作者：
Levine, AJ
影响因子：
19
作者：
Balaburski GM;Hontz RD;Murphy ME
通讯作者：
Murphy ME