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.

Public Health Relevance

Among the many medicinal uses of aspirin (acetyl-salicylate), significant reduction in cancer deaths prompted the National Cancer Institute to put 'establishing careful mechanistic studies that link drug action to changes that alter cancer incidence' as one of the major provocative questions (PQ-5) to be addressed. Therefore, study of salicylate (a plant hormone) signaling in determining cell death and survival in plant immune responses to pathogens may have a direct impact in not only agriculture but also medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM069594-11
Application #
8789164
Study Section
Cellular Signaling and Regulatory Systems Study Section (CSRS)
Program Officer
Sledjeski, Darren D
Project Start
2004-09-01
Project End
2017-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
11
Fiscal Year
2015
Total Cost
$290,241
Indirect Cost
$100,241
Name
Duke University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Gu, Yangnan; Zavaliev, Raul; Dong, Xinnian (2017) Membrane Trafficking in Plant Immunity. Mol Plant 10:1026-1034
Xu, Guoyong; Yuan, Meng; Ai, Chaoren et al. (2017) uORF-mediated translation allows engineered plant disease resistance without fitness costs. Nature 545:491-494
Xu, Guoyong; Greene, George H; Yoo, Heejin et al. (2017) Global translational reprogramming is a fundamental layer of immune regulation in plants. Nature 545:487-490
Withers, John; Dong, Xinnian (2017) Post-translational regulation of plant immunity. Curr Opin Plant Biol 38:124-132
Liu, Lijing; Sonbol, Fathi-Mohamed; Huot, Bethany et al. (2016) Salicylic acid receptors activate jasmonic acid signalling through a non-canonical pathway to promote effector-triggered immunity. Nat Commun 7:13099
Gu, Yangnan; Zebell, Sophia G; Liang, Zizhen et al. (2016) Nuclear Pore Permeabilization Is a Convergent Signaling Event in Effector-Triggered Immunity. Cell 166:1526-1538.e11
Zebell, Sophia G; Dong, Xinnian (2015) Cell-Cycle Regulators and Cell Death in Immunity. Cell Host Microbe 18:402-7
Yang, Li; Li, Bosheng; Zheng, Xiao-yu et al. (2015) Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids. Nat Commun 6:7309
Mammarella, Nicole D; Cheng, Zhenyu; Fu, Zheng Qing et al. (2015) Apoplastic peroxidases are required for salicylic acid-mediated defense against Pseudomonas syringae. Phytochemistry 112:110-21
Zheng, Xiao-Yu; Zhou, Mian; Yoo, Heejin et al. (2015) Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid. Proc Natl Acad Sci U S A 112:9166-73

Showing the most recent 10 out of 27 publications