Structure and Function Analyses of DELLA Interacting Proteins in Arabidopsis

描述（由申请人提供）：二萜类植物激素赤霉素（GA）控制植物的多种发育过程。DELLA蛋白是核转录调节因子，其通过抑制GA反应的各个方面而作为主生长抑制因子起作用。GA与其核受体GID 1（GA不敏感的DWARF 1）的结合增强了GID 1-DELLA相互作用，这反过来又导致DELLA通过泛素-蛋白酶体途径快速蛋白水解，并允许GA响应基因的转录重编程。该GA-GID 1-DELLA信号传导模块似乎通过整合来自其他激素途径[生长素、脱落酸、茉莉酸（JA）和乙烯]的内部信号以及外部生物（病原体）和非生物线索（光条件、冷和盐胁迫）来控制植物生长和发育。最近在拟南芥中的研究表明，DELLA直接结合并调节几个信号通路（光、JA和发育通路）中的关键转录因子/调节子。重要的是，这些DELLA相互作用子属于三个不同的转录因子家族。然而，目前关于DELLA如何调节植物生长的知识只是冰山一角。本提案的目标是阐明新的功能，选择新确定的DELLA相互作用在GA调制的植物发育的遗传和生物化学方法，并确定DELLA如何结合到多个类的相互作用的蛋白质在分子水平上的结构分析。除了转录因子外，一些新的DELLA相互作用物是染色质修饰蛋白或O-GlcNAc转移酶（OGT）。通过OGT对靶蛋白的O-GlcNAc酰化调节动物中的无数细胞途径，但其在植物中的功能知之甚少。这项研究将有助于阐明OGT如何调节植物信号通路。对DELLA及其相互作用调节蛋白的研究将对DELLA调节植物生长的机制做出重要贡献。这项研究还将为调节生长和发育过程中转录重编程和染色质结构的机制提供新的见解，这是控制人类细胞分化和肿瘤发生的共同主题。 癌症的异常细胞增殖通常是由调节适当基因表达的缺陷引起的。这项研究将为控制基因表达以操纵细胞生长和分化的调控机制提供新的见解。

DESCRIPTION (provided by applicant): The diterpenoid phytohormone gibberellin (GA) controls diverse developmental processes in plants. DELLA proteins are nuclear transcriptional regulators, which function as master growth repressors by inhibiting all aspects of GA responses. Binding of GA to its nuclear receptor GID1 (for GA INSENSITIVE DWARF1) enhances the GID1-DELLA interaction, which in turn leads to the rapid proteolysis of DELLA through the ubiquitin-proteasome pathway, and allows transcriptional reprogramming of GA-responsive genes. This GA- GID1-DELLA signaling module appears to control plant growth and development by integrating internal signals from other hormone pathways [auxin, abscisic acid, jasmonic acid (JA) and ethylene], and external biotic (pathogen) and abiotic cues (light conditions, cold and salt stresses). Recent studies in Arabidopsis show that DELLA directly binds to and regulates key transcription factors/regulators in several signaling pathways (light, JA and developmental pathways). Importantly, these DELLA interactors belong to three different families of transcription factors. However, the current knowledge on how DELLA functions to regulate plant growth is only the tip of the iceberg. The goals of this proposal are to elucidate novel functions of selected newly identified DELLA interactors in GA-modulated plant development by genetic and biochemical approaches, and to determine how DELLA binds to multiple classes of interacting proteins at the molecular level by structure analyses. In addition to transcription factors, some of the new DELLA interactors are chromatin modification proteins, or O-GlcNAc transferase (OGT). O-GlcNAcylation of target proteins by OGT regulates a myriad of cellular pathways in animals, but its function in plants is poorly understood. This study will shed light on how OGT regulates signaling pathways in plants. The proposed study on the DELLA and its interacting regulatory proteins will contribute significantly to the mechanism by which DELLA modulates plant growth. This study will also provide new insights into the mechanisms that modulate transcriptional reprogramming and chromatin structure during growth and development, which are a common theme in controlling cell differentiation and tumorigenesis in humans. PUBLIC HEALTH RELEVANCE: Abnormal cell proliferation of Cancer is often caused by defects in regulating proper gene expression. The proposed study will provide new insights into the regulatory mechanisms that control gene expression to manipulate cell growth and differentiation.