Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Republic of Korea.
Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Republic of Korea; Host-Directed Antiviral Research Center, Chonnam National University, Gwangju 61186, Republic of Korea.
Steroids. 2024 Nov;211:109500. doi: 10.1016/j.steroids.2024.109500. Epub 2024 Aug 17.
Estrogen-related receptor gamma (ERRγ) is a member of the ERR orphan nuclear receptor family which possesses three subtypes, α, β, and γ. ERRγ is reportedly predominantly expressed in metabolically active tissues and cells, which promotes positive and negative effects in different tissues. ERRγ overexpression in the liver, pancreas, and thyroid cells is related to liver cancer, oxidative stress, reactive oxygen species (ROS) regulation, and carcinoma. Reduced ERRγ expression in the brain, immune cells, tumor cells, and energy metabolism causes neurological dysfunction, gastric cancer, and obesity. ERRγ is a constitutive receptor; however, its transcriptional activity also depends on co-regulators, agonists, and antagonists, which, when after forming a complex, can play a role in targeting and treating diseases. Moreover, ERRγ has proven crucial in regulating cellular and metabolic activity. However, many functions mediated via ERRγ remain unknown and require further exploration. Hence, considering the importance of ERRγ, this review focuses on the critical findings and interactions between ERRγ and co-regulators, agonists, and antagonists alongside its relationship with downstream and upstream signaling pathways and diseases. This review highlights new findings and provides a path to understanding the current ideas and future studies on ERRγ-mediated cellular activity.
雌激素相关受体 γ（ERRγ）是 ERR 孤儿核受体家族的成员，具有三种亚型，α、β 和 γ。据报道，ERRγ主要在代谢活跃的组织和细胞中表达，在不同的组织中具有促进积极和消极作用。肝脏、胰腺和甲状腺细胞中 ERRγ 的过度表达与肝癌、氧化应激、活性氧（ROS）调节和癌有关。大脑、免疫细胞、肿瘤细胞和能量代谢中 ERRγ 的表达减少会导致神经功能障碍、胃癌和肥胖。ERRγ 是一种组成型受体；然而，其转录活性也依赖于共调节剂、激动剂和拮抗剂，这些调节剂在形成复合物后，可以在靶向和治疗疾病方面发挥作用。此外，ERRγ 已被证明在调节细胞和代谢活性方面至关重要。然而，许多通过 ERRγ 介导的功能仍然未知，需要进一步探索。因此，鉴于 ERRγ 的重要性，本综述重点介绍了 ERRγ 与共调节剂、激动剂和拮抗剂之间的关键发现和相互作用，以及与下游和上游信号通路和疾病的关系。本综述强调了新的发现，并为理解 ERRγ 介导的细胞活性的现有观点和未来研究提供了一条途径。
