Segal Cancer Center, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Division of Experimental Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Int J Mol Sci. 2023 Apr 28;24(9):7983. doi: 10.3390/ijms24097983.
Under low oxygen conditions (hypoxia), cells activate survival mechanisms including metabolic changes and angiogenesis, which are regulated by HIF-1. The estrogen-related receptor alpha (ERRα) is a transcription factor with important roles in the regulation of cellular metabolism that is overexpressed in hypoxia, suggesting that it plays a role in cell survival in this condition. This review enumerates and analyses the recent evidence that points to the role of ERRα as a regulator of hypoxic genes, both in cooperation with HIF-1 and through HIF-1- independent mechanisms, in invertebrate and vertebrate models and in physiological and pathological scenarios. ERRα's functions during hypoxia include two mechanisms: (1) direct ERRα/HIF-1 interaction, which enhances HIF-1's transcriptional activity; and (2) transcriptional activation by ERRα of genes that are classical HIF-1 targets, such as VEGF or glycolytic enzymes. ERRα is thus gaining recognition for its prominent role in the hypoxia response, both in the presence and absence of HIF-1. In some models, ERRα prepares cells for hypoxia, with important clinical/therapeutic implications.
在低氧条件（缺氧）下，细胞激活生存机制，包括代谢变化和血管生成，这些机制受 HIF-1 调节。雌激素相关受体α（ERRα）是一种转录因子，在细胞代谢的调节中具有重要作用，在缺氧时过度表达，表明它在这种情况下在细胞存活中发挥作用。这篇综述列举并分析了最近的证据，这些证据表明 ERRα 作为缺氧基因的调节剂的作用，无论是与 HIF-1 合作还是通过 HIF-1 独立的机制，在无脊椎动物和脊椎动物模型以及生理和病理情况下。ERRα 在缺氧期间的功能包括两种机制：（1）直接 ERRα/HIF-1 相互作用，增强 HIF-1 的转录活性；（2）ERRα 对经典 HIF-1 靶基因如 VEGF 或糖酵解酶的转录激活。因此，ERRα 因其在缺氧反应中的突出作用而受到越来越多的关注，无论是在 HIF-1 存在还是不存在的情况下。在一些模型中，ERRα 为细胞对缺氧做好准备，具有重要的临床/治疗意义。
