Roehrl Michael H A, Wang Julia Y, Wagner Gerhard
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Biochemistry. 2004 Dec 28;43(51):16067-75. doi: 10.1021/bi048232o.
The direct protein-protein interaction between the phosphatase calcineurin and transcription factor NFAT plays important roles in a number of crucial mammalian cell signaling and regulatory events, such as activation of T cells and developmental genetic programs. In this paper, we report on the identification of small organic molecules for the targeted disruption of the NFAT-calcineurin interaction in vitro. In the preceding paper (21), we devise a theoretical and procedural framework for high-throughput fluorescence polarization screens to aid in this effort. The results presented here ground on this work and illustrate the stringency and successful general applicability of our approach. The identified compounds provide valuable molecular tools for probing calcineurin signaling and for the NFAT-specific inhibition of calcineurin in cells and organisms.
磷酸酶钙调神经磷酸酶与转录因子活化T细胞核因子（NFAT）之间的直接蛋白质-蛋白质相互作用在许多关键的哺乳动物细胞信号传导和调节事件中发挥着重要作用，例如T细胞的激活和发育遗传程序。在本文中，我们报告了在体外鉴定用于靶向破坏NFAT-钙调神经磷酸酶相互作用的小分子。在前一篇论文（21）中，我们设计了一个用于高通量荧光偏振筛选的理论和程序框架，以协助这项工作。这里展示的结果基于这项工作，并说明了我们方法的严格性和成功的普遍适用性。所鉴定的化合物为探测钙调神经磷酸酶信号传导以及在细胞和生物体中对钙调神经磷酸酶进行NFAT特异性抑制提供了有价值的分子工具。
