Dynamics of regulatory protein complexes in a changing environment: using the example of plant glucosinolate biosynthesis

转录调控涉及离散数量的转录因子和调控蛋白之间形成复合体，以及随后它们与基因调控DNA区域的相互作用，从而将信号传递给RNA聚合酶-II。这些信号反过来又指示RNA聚合酶是否转录基因以及转录到什么程度。这一建议旨在了解DNA编码的信息如何转化为特定的细胞反应，并研究响应特定的细胞内或细胞外信号而形成转铁蛋白复合体的机制。在研究调控复合体对特定信号的反应时，我们将研究复杂成分之间的相互作用，并揭示解释转录因子通过调节一组选定的基因来激活特定细胞反应的能力的机制。与原核生物不同，真核生物对基因转录的调控不仅在转录水平上，而且在表观、转录后、翻译后和翻译后水平上都受到调控。然而，除了真核生物中的激素受体和酵母中的少数主要代谢物外，关于小分子如何调节转铁蛋白活性或转铁蛋白复合体的组装，人们知之甚少。在这项建议中，我们将以特定类别的植物次生代谢物，即硫代葡萄糖苷(GSLS)为例，阐述属于MYB-bHLH调节复合体的蛋白质的活性是如何对信号分子做出反应的。在这个项目中获得的知识有望以GSL生物合成途径为例，扩展在不断变化的细胞外环境中调节蛋白质-配体组装和拆解动力学的知识。这些结果将促进对GSL生物合成中代谢物信号转导的理解，并有助于理解调节蛋白的活性通常如何被代谢产物控制。该项目将深入了解转录因子在特定环境中激活特定细胞反应的机制。

Transcriptional control involves the formation of complexes between a discrete number of transcription factors (TFs) and regulatory proteins and their subsequent interactions with gene regulatory DNA regions to convey signals to RNA Polymerase-II. These signals, in turn, instruct RNA Polymerase whether to transcribe genes and to what extent. This proposal aims to understand how the information encoded by DNA is transformed into specific cellular responses and to study the mechanisms that underlie the formation of TF complexes in response to specific intra- or extracellular signals. While studying the assembly and disassembly of regulatory complexes in response to specific signals, we will address the interactions between complex components and reveal mechanisms that explain the ability of TFs to activate specific cellular responses by regulating a selected set of genes. In contrast to prokaryotes, the regulation of gene transcription in eukaryotes is controlled not only at the level of transcription, but also epigenetically, post-transcriptionally, translationally and post-translationally. However, with the exception of hormone receptors in eukaryotes and a few primary metabolites in yeast, little is known concerning how small molecules can modulate TF activity or TF complex assembly. In this proposal, we will address how the activity of proteins belonging to the MYB-bHLH regulatory complexes is modulated in response to signalling molecules, using the example of particular class of plant secondary metabolites, namely, glucosinolates (GSLs). Knowledge gained in this project is expected to extend knowledge on the dynamics of regulatory protein-ligand assembly and disassembly in changing extracellular environments, using the example of the GSL biosynthesis pathway. The results will promote the understanding of metabolite signalling in GSL biosynthesis and will contribute to the understanding of how the activity of regulatory proteins can be generally controlled by the metabolic products. The project will generate insight into the mechanisms by which TFs can activate specific cellular responses in a given environment.