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AlphaScreen-based characterization of the bifunctional kinase/RNase IRE1alpha: a novel and atypical drug target

哈o哈o 添加于 2010-5-15 20:19 | 1847 次阅读 | 0 个评论

作者
Bouchecareilh M, Caruso M-E, Roby P, Parent S, Rouleau N, Taouji S, Pluquet O, Bosse R, Moenner M, Chevet E
摘要
Assay technologies that were originally developed for high-throughput screening (HTS) have recently proven useful in drug discovery for activities located upstream (target identification and validation) and downstream (ADMET) of HTS. Here the authors investigated and characterized the biological properties of a novel target, IRE1alpha, a bifunctional kinase/RNase stress sensor of the endoplasmic reticulum (ER). They have developed a novel assay platform using the HTS technology AlphaScreen to monitor the dimerization/oligomerization and phosphorylation properties of the cytosolic domain of IRE1alpha. They show in vitro that dimerization/oligomerization of the cytosolic domain of IRE1 correlated with the autophosphorylation ability of this domain and its endoribonuclease activity toward XBP1 mRNA. Using orthogonal in vitro and cell-based approaches, the authors show that the results obtained using AlphaScreen were biologically relevant. Preliminary characterization of assay robustness indicates that both AlphaScreen assays should be useful in HTS for the identification of IRE1 activity modulators.
详细资料
- 文献种类:期刊
- 期刊名称: Journal of Biomolecular Screening : the Official Journal of the Society for Biomolecular Screening
- 期刊缩写: J Biomol Screen
- 期卷页: 2010年第15卷第4期 406-417页
- 地址: 1Inserm, U889, Avenir, Bordeaux, France
- ISBN: 1087-0571
- 备注:PMID:20237204
标签

内质网应激炎性肠病病因
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