Fluorescence polarization assay and inhibitor design for MDM2/p53 interaction
Fluorescence polarization assay and inhibitor design for MDM2/p53 interaction
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DOI：
10.1016/j.ab.2004.03.009
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发表时间：
2004-08-01
影响因子：
2.9
通讯作者：
Windsor, W
中科院分区：
文献类型：
--
作者：
Zhang, RM;Mayhood, T;Windsor, W
MDM 2是肿瘤抑制蛋白p53的重要负调节因子，该蛋白调节包括MDM 2在内的许多基因的表达。这种自动调节回路的微妙平衡对于基因组的维持和细胞周期和凋亡的控制至关重要。由于ARF基因座的扩增/过表达或突变失活，MDM 2过度活性抑制野生型p53的功能，并可导致多种癌症的发展。因此，抗MDM 2疗法的开发可以恢复肿瘤细胞中的正常p53功能并诱导生长抑制和凋亡。我们在这里报告了一种新的高通量荧光偏振结合测定法及其在等级排序小分子抑制剂中的应用，该抑制剂阻断MDM 2与p53衍生的荧光肽的结合。爱思唯尔公司出版
MDM2 is an important negative regulator of the tumor suppressor protein p53 which regulates the expression of many genes including MDM2. The delicate balance of this autoregulatory loop is crucial for the maintenance of the genome and control of the cell cycle and apoptosis. MDM2 hyperactivity, due to amplification/overexpression or mutational inactivation of the ARF locus, inhibits the function of wild-type p53 and can lead to the development of a wide variety of cancers. Thus, the development of anti-MDM2 therapies may restore normal p53 function in tumor cells and induce growth suppression and apoptosis. We report here a novel high-throughput fluorescence polarization binding assay and its application in rank ordering small-molecule inhibitors that block the binding of MDM2 to a p53-derived fluorescent peptide. Published by Elsevier Inc.