神经生长因子IB
核受体
孤儿受体
生物
兴奋剂
细胞生物学
受体
转录因子
癌症研究
分子生物学
生物化学
基因
作者
Yan-yan Zhan,Xiping Du,Hang-zi Chen,Jingjing Liu,Bixing Zhao,Huang Dan-hong,Guideng Li,Qingyan Xu,Mingqing Zhang,Bart C. Weimer,Dong Chen,Zhe Cheng,Lianru Zhang,Qinxi Li,Shaowei Li,Zhuo Zheng,Shuai Song,Yipeng Huang,Zhiyun Ye,Wen‐Jin Su,Sheng Lin,Yuemao Shen,Qiao Wu
摘要
Nuclear orphan receptor Nur77 has important roles in many biological processes. However, a physiological ligand for Nur77 has not been identified. Here, we report that the octaketide cytosporone B (Csn-B) is a naturally occurring agonist for Nur77. Csn-B specifically binds to the ligand-binding domain of Nur77 and stimulates Nur77-dependent transactivational activity towards target genes including Nr4a1 (Nur77) itself, which contains multiple consensus response elements allowing positive autoregulation in a Csn-B-dependent manner. Csn-B also elevates blood glucose levels in fasting C57 mice, an effect that is accompanied by induction of multiple genes involved in gluconeogenesis. These biological effects were not observed in Nur77-null (Nr4a1-/-) mice, which indicates that Csn-B regulates gluconeogenesis through Nur77. Moreover, Csn-B induced apoptosis and retarded xenograft tumor growth by inducing Nur77 expression, translocating Nur77 to mitochondria to cause cytochrome c release. Thus, Csn-B may represent a promising therapeutic drug for cancers and hypoglycemia, and it may also be useful as a reagent to increase understanding of Nur77 biological function.
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