School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Pharmacol Res. 2022 Mar;177:106013. doi: 10.1016/j.phrs.2021.106013. Epub 2021 Nov 29.
Ferroptosis is a type of lipid peroxidation-induced cell death that can be regulated in various ways, from changing the activity of antioxidant enzymes to the levels of transcription factors. The p53 tumor suppressor gene is the "guardian of the genome" and is involved in controlling cell survival and division under various pressures. In addition to its effects on apoptosis, autophagy, and cell cycle, p53, through the way of transcription dependent or independent two-way, also regulates the biological processes of tumor cell sensitivity to ferroptosis, including the metabolism of amino acids, nicotinamide adenine dinucleotide phosphate, and lipid peroxidation, as well as the biosynthesis of glutathione, phospholipids, NADPH and coenzyme Q10. As reviewed here, we summarized the metabolic network of p53 and its signaling pathway in regulating ferroptosis and elucidated possible factors and potential clinical application of p53 regulating ferroptosis. This review will provide a basis for further understanding the role of p53 in tumor ferroptosis and new strategies for cancer therapeutic avenues.
铁死亡是一种脂质过氧化诱导的细胞死亡，可以通过改变抗氧化酶的活性到转录因子的水平等多种方式进行调节。p53 肿瘤抑制基因是“基因组的守护者”，参与控制细胞在各种压力下的存活和分裂。除了对细胞凋亡、自噬和细胞周期的影响外，p53 还通过转录依赖或独立的双向方式调节肿瘤细胞对铁死亡敏感性的生物学过程，包括氨基酸、烟酰胺腺嘌呤二核苷酸磷酸和脂质过氧化的代谢，以及谷胱甘肽、磷脂、NADPH 和辅酶 Q10 的生物合成。在这里我们综述了 p53 的代谢网络及其在调控铁死亡中的信号通路，并阐明了 p53 调控铁死亡的可能因素和潜在的临床应用。这篇综述将为进一步了解 p53 在肿瘤铁死亡中的作用以及癌症治疗途径的新策略提供依据。
