Novel auxin signaling components and pathways.

新型生长素信号传导成分和途径。

• 批准号: 10614965
• 负责人: MARK A ESTELLE
• 金额: $ 39.5万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10614965
• 关键词: Address; Angiosperms; Arabidopsis; Architecture; Auxins; Cell physiology; ChIP-seq; Chromatin; Collaborations; Complex; Defect; Developmental Process; Disease; Droughts; Exclusion; F Box Domain; Family; Genes; Genetic; Genetic Transcription; Glucosinolates; Goals; Grant; Growth; Health; Human; Investigation; Malignant Neoplasms; Mediating; Molecular; Mouse-ear Cress; Orthologous Gene; Pathway interactions; Physcomitrella; Physiological Processes; Plant Growth Regulators; Plants; Process; Proteins; Regulation; Regulator Genes; Role; Signal Transduction; Specificity; System; Transcription Repressor; Ubiquitin; cell growth regulation; derepression; experimental study; gene regulatory network; interest; member; multicatalytic endopeptidase complex; novel; plant growth/development; proteostasis; receptor; recruit; response; transcription factor; ubiquitin-protein ligase; virtual

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.

项目摘要 植物激素生长素几乎调节植物生长和发育的所有方面。我们和其他人已经 研究表明，生长素促进称为Aux/IAA蛋白的转录抑制因子的降解，通过一种新的途径， 家族E3连接酶称为SCFTIR 1/AFB。生长素被一个由TIR 1/AFB蛋白，F- box亚基和Aux/IAA蛋白。这种复合物的形成促进了 Aux/IAA蛋白和ARF转录因子的转录。虽然这条基本途径 虽然生长素的作用机制已经建立，但它如何调节如此广泛的发育和生理过程尚不清楚。 目前，在我们的RO 1赠款的第二年，我们正在调查这个广泛的问题，使用两个 互补的遗传系统;开花植物拟南芥和基地植物 小立碗藓我们的研究重点是TIR 1/AFB蛋白的功能，Aux/IAA的调控， 水平和生长素信号网络的架构。我们最近证明了6个成员中的5个 拟南芥中的TIR 1/AFB家族以重叠的方式起作用。第六个成员，AFB 1，在小说中发挥作用 转录非依赖性生长素反应途径。此外，我们最近的ChIPseq实验表明， TIR 1/AFB蛋白（不包括AFB 1）被生长素募集到与生长素调节基因相邻的染色质上。 我们推测，这种机制允许快速去抑制生长素反应基因。我们也做 我们对Aux/IAA蛋白及其调控的理解取得了重大进展。我们最近发现 Aux/IAA是E3连接酶CRL 3-BPM的底物。BPM是直系同源物 人类SPOP蛋白质。此外，我们发现Aux/IAA基因是调控节点， 整合环境信号与生长素基因调控网络。例如，我们已经证明， 某些Aux/IAA蛋白质通过调节称为生长素的次级产物的水平来赋予耐旱性。 芥子油苷这些化合物促进气孔关闭和耐旱性。未来5年，我们将 继续研究生长素信号传导的分子基础，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SCFTIR 1/AFB对Aux/IAA水平的调节作用。 CRL3-BPM我们的长期目标之一是了解AFB、Aux/IAA和ARF的特异性 在索尔克研究所与乔·埃克的实验室合作研究蛋白质。这项工作将包括调查 AFB募集到染色质。这些研究解决了细胞调节中的一些关键问题， 对人类健康有重要影响。