2. Academic Validation
  3. Cytosporone B is an agonist for nuclear orphan receptor Nur77

Cytosporone B is an agonist for nuclear orphan receptor Nur77

  • Nat Chem Biol. 2008 Sep;4(9):548-56. doi: 10.1038/nchembio.106.
Yanyan Zhan 1,  Xiping Du,  Hangzi Chen,  Jingjing Liu,  Bixing Zhao,  Danhong Huang,  Guideng Li,  Qingyan Xu,  Mingqing Zhang,  Bart C Weimer,  Dong Chen,  Zhe Cheng,  Lianru Zhang,  Qinxi Li,  Shaowei Li,  Zhonghui Zheng,  Siyang Song,  Yaojian Huang,  Zhiyun Ye,  Wenjin Su,  Sheng-Cai Lin,  Yuemao Shen,  Qiao Wu
Affiliations

Affiliation

  • 1 Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, 422 South Siming Road, Xiamen, Fujian 361005, China.
PMID: 18690216 DOI: 10.1038/nchembio.106
Abstract

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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