文章：

铁致细胞死亡中的转录因子

Transcription factors in ferroptotic cell death 

原文发布日期：2020-03-03 

英文摘要：

Ferroptosis, a form of regulated cell death, is characterized by an excessive degree of iron accumulation and lipid peroxidation. Although it was originally identified only in cells expressing a mutant RAS oncogene, ferroptosis has also been found in normal cells following treatment by small molecules (e.g., erastin and RSL3) or drugs (e.g., sulfasalazine, sorafenib, and artesunate), which target antioxidant enzyme systems, especially the amino acid antiporter system xc− and the glutathione peroxidase GPX4. Dysfunctional ferroptosis is implicated in various physiological and pathological processes (e.g., metabolism, differentiation, and immunity). Targeting the ferroptotic network appears to a new treatment option for diseases or pathological conditions (e.g., cancer, neurodegeneration, and ischemia reperfusion injury). While the molecular machinery of ferroptosis remains largely unknown, several transcription factors (e.g., TP53, NFE2L2/NRF2, ATF3, ATF4, YAP1, TAZ, TFAP2C, SP1, HIF1A, EPAS1/HIF2A, BACH1, TFEB, JUN, HIC1, and HNF4A) play multiple roles in shaping ferroptosis sensitivity through either transcription-dependent or transcription-independent mechanisms. In this review, we summarize recent progress in understanding the transcriptional regulation underlying ferroptotic cell death, and discuss how it has provided new insights into cancer therapy. 

摘要翻译： 

铁死亡是一种受调控的细胞死亡形式，其典型特征是过度的铁积累和脂质过氧化。虽然最初仅在表达突变RAS癌基因的细胞中发现，但后续研究证实，经靶向抗氧化酶系统（特别是氨基酸反向转运系统xc−和谷胱甘肽过氧化物酶GPX4）的小分子（如erastin和RSL3）或药物（如柳氮磺吡啶、索拉非尼和青蒿琥酯）处理后，正常细胞也会发生铁死亡。铁死亡功能失调与多种生理和病理过程（如代谢、分化和免疫）密切相关。靶向铁死亡网络似乎为疾病或病理状态（如癌症、神经退行性病变和缺血再灌注损伤）提供了新的治疗选择。虽然铁死亡的分子机制仍 largely 未知，但若干转录因子（如TP53、NFE2L2/NRF2、ATF3、ATF4、YAP1、TAZ、TFAP2C、SP1、HIF1A、EPAS1/HIF2A、BACH1、TFEB、JUN、HIC1和HNF4A）通过转录依赖或非转录依赖机制在调控铁死亡敏感性中发挥多重作用。本文综述了铁死亡细胞转录调控机制的最新研究进展，并探讨了该领域如何为癌症治疗提供新视角。

原文链接：

Transcription factors in ferroptotic cell death