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Title[redir]:
Cytosporone B is an agonist for nuclear orphan receptor Nur77 | Nature Chemical Biology
Description:
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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article, scholar, cas, google, nature, nuclear, cell, receptor, orphan, receptors, biol, access, chem, cancer, chen, nra, function, content, csnb, cookies, apoptosis, cells, mol, science, privacy, data, huang, lin, open, binding, scl, supplementary, information, biology, agonist, zhan, liu, zhang, genes, glucose, tcell, nat, human, molecular, university, research, experiments, group, performed, advertising,
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nature portfolio cancer research center nature chemical biology permissions reprints privacy policy peroxisome proliferator-activated receptor-gamma advertising nur77/nr4a1 mediates trans-activation social media nature 367 nature 423 nature 395 nature transforming growth factor-β nuclear receptor-independent pathways ligand-independent nuclear receptors personal data retinoic acid sensitivity t-cell hybrid require af-1-dependent coactivator recruitment data protection springerlink instant access orphan nuclear receptors human glucocorticoid receptor nuclear receptor-dependent orphan receptor tr3 permissions nurr1 ligand-binding domain china nuclear receptor superfamily development multiple genes involved disease-modifying effects orphan receptors nur77 tr3 nuclear export nuclear hormone receptors nuclear receptors nr4a3 cheung kong scholar chitin transport estrogen receptor beta privacy tumor cell engineering t-cell receptor unified nomenclature system energy terms yuemao shen qiao wu sheng-cai lin article zhan receptor-selective retinoids
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headline:Cytosporone B is an agonist for nuclear orphan receptor Nur77
description:
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-Bâdependent 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 (Nr4a1â/â) 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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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-Bâdependent 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 (Nr4a1â/â) 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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