Journal ArticleDOI
Cytosporone B is an agonist for nuclear orphan receptor Nur77
Yan-yan Zhan,Xiping Du,Hang-zi Chen,Jingjing Liu,Bi-xing Zhao,Danhong Huang,Guideng Li,Qingyan Xu,Ming-Qing 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 +22 more
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TLDR
The octaketide cytosporone B (Csn-B) is a naturally occurring agonist for Nur77 that induced apoptosis and retarded xenograft tumor growth by inducing Nur77 expression, translocating Nur77 to mitochondria to cause cytochrome c release and may be useful as a reagent to increase understanding of Nur77 biological function.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.read more
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The Role of Histone Acetylation in Memory Formation and Cognitive Impairments
Lucia Peixoto,Ted Abel +1 more
TL;DR: A general model by which corepressors and coactivators regulate histone acetylation during memory storage is outlined and how the recent advances in high-throughput sequencing have the potential to radically change the understanding of how epigenetic control operates in the brain is discussed.
Journal ArticleDOI
Minireview: Nuclear Hormone Receptor 4A Signaling: Implications for Metabolic Disease
TL;DR: The preliminary studies reviewed in this manuscript suggest that therapeutic exploitation of the NR4A subgroup may show utility against dyslipidemia, obesity, diabetes, and cardiovascular disease.
Journal ArticleDOI
Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis
Katrin Palumbo-Zerr,Pawel Zerr,Alfiya Distler,Judith Fliehr,Rossella Mancuso,Jingang Huang,Dirk Mielenz,Michal Tomcik,Barbara G. Fürnrohr,Carina Scholtysek,Clara Dees,Christian Beyer,Gerhard Krönke,Daniel Metzger,Oliver Distler,Georg Schett,Jörg H W Distler +16 more
TL;DR: The data demonstrate a regulatory role of NR4A1 in TGF-β signaling and fibrosis, providing the first proof of concept for targeting NR3A2 in fibrotic diseases and a potential target for anti-fibrotic therapies.
Journal ArticleDOI
Grading the commercial optical biosensor literature-Class of 2008: 'The Mighty Binders'.
Rebecca L. Rich,David G. Myszka +1 more
TL;DR: This work grades every paper published in 2008 on a scale from A to F and outlines what features make a biosensor article fabulous, middling or abysmal and focuses on a few experimental, analysis and presentation mistakes that are alarmingly common.
Journal ArticleDOI
Target identification among known drugs by deep learning from heterogeneous networks.
Xiangxiang Zeng,Siyi Zhu,Weiqiang Lu,Zehui Liu,Jin Huang,Yadi Zhou,Jiansong Fang,Yin Huang,Yin Huang,Huimin Guo,Lang Li,Bruce D. Trapp,Ruth Nussinov,Ruth Nussinov,Charis Eng,Joseph Loscalzo,Feixiong Cheng,Feixiong Cheng,Feixiong Cheng +18 more
TL;DR: DeepDTnet offers a powerful network-based deep learning methodology for target identification to accelerate drug repurposing and minimize the translational gap in drug development.
References
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