Novel auxin signaling components and pathways.

项目摘要 植物激素生长素几乎调控植物生长发育的方方面面。我们和其他人有 证明生长素通过一种途径促进称为AUX/IAA蛋白的转录抑制物的降解 E3家族连接酶称为SCFTIR1/AFB。生长素是由TIR1/AFB蛋白组成的共同受体感知的，F- E3的Box亚基和AUX/IAA蛋白。这种复合体的形成促进了 AUX/IAA蛋白和ARF转录因子的转录。虽然这条基本路径很好 目前还不清楚生长素是如何调节如此广泛的发育和生理过程的。 目前在我们RO1拨款的第二年，我们正在使用两个 互补的遗传系统；开花植物拟南芥和基本陆地植物 小球藻Physcomitrella patens.我们的重点是TIR1/AFB蛋白的功能，AUX/IAA的调节 水平，以及生长素信令网络的体系结构。我们最近证明了6名成员中的5名 TIR1/AFB家族在拟南芥中的作用是重叠的。第六个成员AFB1在一部小说中发挥作用 不依赖转录的生长素反应途径。此外，我们最近的ChIPseq实验表明 TIR1/AFB蛋白(不包括AFB1)被生长素招募到与生长素调节基因相邻的染色质中。 我们推测，这种机制允许生长素反应基因的快速降压。我们还制作了 我们对AUX/IAA蛋白及其调控的了解取得了重大进展。我们最近发现 除了SCFTIR1/AFB外，AUX/IAA还是称为CRL3-BPM的E3连接酶的底物。BPM是直系同源的 人类SPOP蛋白的。此外，我们还证明了AUX/IAA基因是调节节点 将环境信号与生长素基因调控网络整合。例如，我们已经展示了 某些AUX/IAA蛋白通过调节称为 硫代葡萄糖苷。这些化合物促进气孔关闭和抗旱性。在接下来的5年里，我们将 继续研究生长素信号的分子基础，并表征基于生长素的调节 控制植物生长和发育的网络。我们对新的快速生长素反应非常感兴趣 途径及其在生长中的作用。我们还将研究SCFTIR1/AFB对AUX/IAA水平的调节 和CRL3-BPM。我们的长期目标之一是了解AFB、AUX/IAA和ARF的特殊性 蛋白质，与乔·埃克在索尔克研究所的实验室合作。这项努力将包括调查 AFB招募到染色质。这些研究涉及细胞调节中的一些关键问题，并将 对人类健康有重要影响。

Project Summary The plant hormone auxin regulates virtually all aspects of plant growth and development. We and others have demonstrated that auxin promotes degradation of transcriptional repressors called Aux/IAA proteins, via a family E3 ligases called SCFTIR1/AFB. Auxin is perceived by a co-receptor consisting of a TIR1/AFB protein, the F- box subunit of the E3, and the Aux/IAA protein. The formation of this complex promotes degradation of the Aux/IAA protein and transcription by ARF transcription factors. Although this basic pathway is well established, it is not clear how auxin regulates such a wide range of developmental and physiological processes. Currently in the second year of our RO1 grant, we are investigating this broad question using two complementary genetic systems; the flowering plant Arabidopsis thaliana, and the basal land plant Physcomitrella patens. Our focus has been on the function of the TIR1/AFB proteins, regulation of Aux/IAA level, and the architecture of the auxin signaling network. We recently demonstrated that 5 of the 6 member TIR1/AFB family in Arabidopsis act in an overlapping fashion. The 6th member, AFB1, functions in a novel transcription-independent auxin response pathway. Further, our recent ChIPseq experiments indicate that TIR1/AFB proteins (excluding AFB1) are recruited by auxin to chromatin adjacent to auxin-regulated genes. We speculate that this mechanism permits rapid de-repression of auxin responsive genes. We also made significant advances in our understanding of Aux/IAA proteins and their regulation. We recently discovered that Aux/IAA are substrates of E3 ligases called CRL3-BPM, in addition to SCFTIR1/AFB. The BPMs are orthologs of the human SPOP proteins. In addition, we showed that the Aux/IAA genes are regulatory nodes that integrate environmental signals with the auxin gene regulatory network. For example, we have shown that certain Aux/IAA proteins confer drought tolerance by regulating the levels of secondary products called glucosinolates. These compounds promote stomatal closure and drought tolerance. In the next 5 years we will continue to investigate the molecular basis of auxin signaling and to characterize the auxin-based regulatory networks that control plant growth and development. We are very interested in the novel rapid auxin response pathway and its role in growth. We will also investigate the regulation of Aux/IAA levels by both SCFTIR1/AFB and CRL3-BPM. One of our long-term goals is understand the specificity of the AFB, Aux/IAA, and ARF proteins in collaboration with Joe Ecker's lab at the Salk Institute. This effort will include the investigation of AFB recruitment to chromatin. These studies address a number of key issues in cellular regulation and will have important implications for human health.