Identification of inhibitors of auxin transcriptional activation by means of chemical genetics in Arabidopsis
Identification of inhibitors of auxin transcriptional activation by means of chemical genetics in Arabidopsis
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DOI：
10.1073/pnas.0404312101
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发表时间：
2004-10-12
影响因子：
11.1
通讯作者：
Theologis, A
中科院分区：
文献类型：
--
作者：
Armstrong, JI;Yuan, S;Theologis, A
生长素通过直接转录调控和与其他植物激素的协同信号传导调节多种植物发育途径。遗传和生化方法已经阐明了生长素调控网络的几个方面；然而，感知机制和随后的信号事件在很大程度上仍未被描述。为了阐明未知的中间产物，我们开发了一种高通量筛选方法来鉴定拟南芥中生长素信号传导的小分子抑制剂。对10,000种化合物的分析揭示了几种有效的铅结构，这些结构可以消除生长素诱导的报告基因的转录。研究发现，三种化合物干扰生长素调控的生长素/吲哚-3-乙酸转录因子的蛋白水解，两种化合物的表型表明生长素反应发生改变，包括损害根发育。微阵列分析被用来证明两种最有效的分子的机制相似性。这一策略有望为发现生长素信号网络的未知成分以及研究生长素在植物发育各个阶段的参与提供强有力的工具。
Auxin modulates diverse plant developmental pathways through direct transcriptional regulation and cooperative signaling with other plant hormones. Genetic and biochemical approaches have clarified several aspects of the auxin-regulated networks; however, the mechanisms of perception and subsequent signaling events remain largely uncharacterized. To elucidate unidentified intermediates, we have developed a high-throughput screen for identifying small molecule inhibitors of auxin signaling in Arabidopsis. Analysis of 10,000 compounds revealed several potent lead structures that abrogate transcription of an auxin-inducible reporter gene. Three compounds were found to interfere with auxin-regulated proteolysis of an auxin/indole-3-acetic acid transcription factor, and two impart phenotypes indicative of an altered auxin response, including impaired root development. Microarray analysis was used to demonstrate the mechanistic similarities of the two most potent molecules. This strategy promises to yield powerful tools for the discovery of unidentified components of the auxin-signaling networks and the study of auxin's participation in various stages of plant development.