Dynamic regulation of salicylic acid biosynthesis & perception in plant immunity

描述（由申请人提供）：水杨酸（SA）及其衍生物，如阿司匹林，具有一长串的药用作用，不仅包括退烧和缓解疼痛，而且还包括预防心血管疾病和显著减少各种癌症和II型糖尿病症状造成的死亡。然而，水杨酸盐广泛的药物作用背后的分子机制尚不完全清楚。SA是一种控制植物免疫应答系统获得性抗性（SAR）的植物激素。SAR是一种广谱抗性，可由导致程序性细胞死亡（PCD）的局部病原体攻击或外源应用SA诱导。SA信号需要转录辅助因子NPR1蛋白的作用。然而，尽管经过多年的研究，主要问题仍然存在：(1)植物中SA的合成是如何调节的；(2)SA的受体是什么。通过Aim 1，将研究昼夜节律钟成分CHE和病原体效应物特异性靶向的转录因子对SA生物合成基因的调控。该假说认为，植物中的SA水平与细胞氧化还原状态密切相关，而细胞氧化还原状态影响生物钟、NPR1核易位和抗病性。目的2将重点研究NPR1类似物NPR3和NPR4作为SA受体的特性，这两种含有Cullin 3e3泛素连接酶的btb结构域适配器。SA特异性结合NPR3和NPR4，调节它们与NPR1的相互作用，控制蛋白酶体介导的NPR1降解。这些相互作用的动力学将在病原体攻击时在局部和全身组织中进行检查，以证明NPR1在感染细胞中降解以允许病原体效应物触发PCD和抗性，以及NPR1在感染部位周围细胞中积累以防止PCD扩散并促进SAR的假设。NPR1抑制PCD的机制将通过研究具有抗PCD活性的NPR1转录靶点来测试。了解植物中SA的产生和感知将为水杨酸盐的药用作用提供新的见解，因为SA影响细胞氧化还原和细胞死亡和生存，这是所有生物的基本过程。

DESCRIPTION (provided by applicant): Salicylic acid (SA) and derivatives, such as aspirin, have a long list of medicinal effects, which include not only fever reduction and pain relief, but also prevention of cardiovascular diseases and significant reduction of deaths by various cancers and symptoms of type II diabetes. However, the molecular mechanisms underlying this wide range of medicinal effects of salicylates are not completely known. SA is a plant hormone that controls the plant immune response, systemic acquired resistance (SAR). SAR is a broad-spectrum resistance that can be induced by a local pathogen challenge that results in programmed cell death (PCD) or by exogenous application of SA. SA signaling requires the function of the transcription cofactor NPR1 protein. However, despite years of research, major questions remain with regard to (1) how SA synthesis is regulated in plants and (2) what the receptor is for SA. Through Aim 1, the regulation of SA biosynthesis genes by a circadian clock component, CHE, and by transcription factors specifically targeted by pathogen effectors will be studied. The hypothesis that SA levels in plants are intimately linked with the cellular redox stat which influences the circadian clock, NPR1 nuclear translocation, and disease resistance will be tested. Aim 2 will focus on the characterization of NPR1 paralogs, NPR3 and NPR4, two BTB-domain containing adaptors for Cullin 3 E3 ubiquitin ligase, as SA receptors. SA binds to NPR3 and NPR4 specifically and regulates their interactions with NPR1 to control proteasome-mediated degradation of NPR1. The dynamics of these interactions will be examined in both local and systemic tissues upon pathogen challenge to prove the hypothesis that NPR1 is degraded in the infected cells to allow pathogen effectors-triggered PCD and resistance, and that NPR1 accumulates in the cells surrounding the infection site to prevent the spread of PCD and to promote SAR. The mechanism by which NPR1 inhibits PCD will be tested through study of NPR1-transcriptional targets with anti-PCD activities. Understanding SA production and perception in plants will provide new insights into the medicinal effects of salicylates because SA affects cellular redox and cell death and survival, which are processes fundamental to all living organisms.