Effect of Nitric Oxide on Gene Transcription – S-Nitrosylation of Nuclear Proteins
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REVIEW ARTICLE published: 01 August 2013 doi: 10.3389/fpls.2013.00293 Effect of nitric oxide on gene transcription – S-nitrosylation of nuclear proteins Alexander Mengel, Mounira Chaki, Azam Shekariesfahlan and Christian Lindermayr* Institute of Biochemical Plant Pathology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany Edited by: Nitric oxide (NO) plays an important role in many different physiological processes in plants. Emmanuel Baudouin, Université It mainly acts by post-translationally modifying proteins. Modification of cysteine residues Pierre et Marie Curie - Paris 6, France termed as S-nitrosylation is believed to be the most important mechanism for transduction Reviewed by: of bioactivity of NO. The first proteins found to be nitrosylated were mainly of cytoplasmic Georgia Tanou, Aristotle University of Thessaloniki, Greece origin or isolated from mitochondria and peroxisomes. Interestingly, it was shown that David Wendehenne, University of redox-sensitive transcription factors are also nitrosylated and that NO influences the redox- Burgundy, France dependent nuclear transport of some proteins.This implies that NO plays a role in regulating *Correspondence: transcription and/or general nuclear metabolism which is a fascinating new aspect of NO Christian Lindermayr, Institute of signaling in plants. In this review, we will discuss the impact of S-nitrosylation on nuclear Biochemical Plant Pathology, Helmholtz Zentrum München – plant proteins with a focus on transcriptional regulation, describe the function of this German Research Center for modification and draw also comparisons to the animal system in which S-nitrosylation Environmental Health, Ingolstädter of nuclear proteins is a well characterized concept. Landstrasse 1, 85764 Neuherberg, Germany Keywords: protein S-nitrosylation, nitric oxide, post-translational modification, nuclear proteins, redox- e-mail: lindermayr@helmholtz- modification muenchen.de INTRODUCTION There are three important NO-dependent modifications: metal Nitric oxide (NO) is a small, highly reactive gaseous radical. nitrosylation, tyrosine nitration, and cysteine S-nitrosylation. Although it is cytotoxic in high concentrations, NO plays a key In a direct reaction termed metal nitrosylation, NO (Lewis base) role as a biological messenger in all kingdoms. In plants, it is binds to the transition metal (Lewis acid) of metalloproteins yield- implicated in various physiological processes like flowering, stom- ing a metal–nitrosyl complex. One example from mammals is the atal closure, germination, root development, gravitropism, and binding of NO to the heme center of soluble guanylate cyclase responses to abiotic and biotic stresses (Delledonne et al., 1998; which activates this enzyme by inducing conformational changes Durner et al., 1998; Garcia-Mata and Lamattina, 2002; Pagnussat and this in turn leads to the production of cyclic GMP (Russwurm et al., 2002; He et al., 2004; Hu et al., 2005; Lombardo et al., 2006; and Koesling, 2004). De Michele et al., 2009; Sirova et al., 2011; Tanou et al., 2012). Reactive nitrogen species can modify the activity of proteins Due to its instable nature, NO has a very rich chemistry. by covalently binding to tyrosine and cysteine residues. Tyrosine Besides direct dative binding to metal ions NO can further react nitration refers to the addition of a nitro group to susceptible with superoxide and molecular oxygen, resulting in the forma- tyrosine residues in ortho position to the hydroxyl group thus tion of peroxynitrite and dinitrogen trioxide N2O3 (or higher leading to 3-nitrotyrosine. The main nitrating species is peroxyni- oxides like NO2), respectively. Moreover, adding or removing trite which is produced in a diffusion controlled reaction between one electron from the antibonding highest occupied molecular NO and superoxide (Ferrer-Sueta and Radi, 2009). Tyrosine nitra- orbital by reducing or oxidizing chemicals yields nitroxyl anion tion was originally considered to be indicative for oxidative and (NO−) and nitrosonium cation (NO+). Collectively, these species nitrosative stress but evidence accumulates that this modification are referred to as reactive nitrogen species (RNS) each having also has a signaling function in plant cells (Cecconi et al., 2009; distinct chemical properties leading to numerous reactions with Gaupels et al., 2011). biological molecules like lipids, carbohydrates, nucleic acids, and S-nitrosylation of protein cysteine residues is believed to be proteins. Although most of these reactions were assumed to be the most important mechanism for transduction of bioactivity of indicative for nitrosative stress in the past, it has become clear that NO in plants. The formation of nitrosothiols is still debated. The some of these RNS also function as important redox-signaling direct reaction of thiol groups with NO is too slow to occur in vivo, molecules in the cell by binding covalently to target proteins instead it is assumed that N2O3 is the main nitrosylating species in (Suzuki et al., 2012; Yun et al., 2012). This as redox-signaling aerobic conditions although the formation of dinitrogen trioxide termed mechanism should not be considered as a discrete set of is controversially discussed (Folkes and Wardman, 2004; Ridnour signaling cascades. Rather, the cell should be seen as set of com- et al., 2004). Other RNS described to mediate S-nitrosothiol for- partments each having distinct redox-sensitive proteins as well as mation are nitrosonium and nitroxyl ions (Ridnour et al., 2004). redox buffering capacities. Changes in the redox potential of these Nitroso groups can also be transferred between thiols in a process compartments could then influence other signaling pathways by termed as transnitrosylation. Transnitrosylation occurs between modifying redox-sensitive proteins (Foyer and Noctor, 2013). proteins and between proteins and low molecular weight SNOs www.frontiersin.org August 2013 | Volume 4 | Article 293 | 1 “fpls-04-00293” — 2013/7/30 — 17:42 — page1—#1 Mengel et al. S-nitrosylation of nuclear proteins (e.g., S-nitrosylated glutathione GSNO) in animals; in plants, post-translational modifications like oxidation to sulfinic acid, however, evidence for this mechanism is lacking (Hogg, 2002; S-glutathionylation, or S-nitrosylation. Each of these modifica- Nakamura and Lipton, 2013). Enzymatic denitrosylation is medi- tions affects binding affinity and specificity of OxyR to DNA ated by GSNO reductase (GSNOR) and thioredoxins (Trx), both thus resulting in distinct transcriptional responses (Marshall et al., proteins are crucial for maintaining SNO-homeostasis (Sakamoto 2000). Besides regulation of DNA-binding, S-nitrosylation of et al., 2002; Feechan et al., 2005; Sengupta and Holmgren, 2013). nuclear proteins could also affect their subcellular localization or Initial proteomic screens for S-nitrosylated proteins in regulate the association with binding partners thereby modulating A. thaliana revealed 53 mainly cytoplasmic proteins but this num- transcription and/or general nuclear metabolism. In animals, for ber increased drastically over the last years (Lindermayr et al., instance, S-nitrosylation of the nuclear export receptor CRM1 2005). Up to date several screens targeting the proteomes of differ- (karyopherin chromosomal region maintenance 1) leads to a ent organelles like mitochondria and peroxisomes identified more decrease in the export rate and a subsequent nuclear accumula- than 250 candidate proteins to be S-nitrosylated involved in a wide tion of its target protein Nrf2, an antioxidant transcription factor range of physiological processes ranging from stress response to (Wang et al., 2009). The possible modes of action of NO on gene metabolism (Kovacs and Lindermayr, 2013; Lounifi et al., 2013). transcription are shown in Figure 1. Interestingly, microarray analysis and amplified fragment-length In this review, we will summarize the current knowledge about polymorphism (AFLP) transcript profiling of plants treated with S-nitrosylated nuclear plant proteins. What is the impact and func- gaseous NO and sodium nitroprusside, respectively, showed that tion of this post-translational modification? Comparisons to the NO leads to changes in the transcriptome of Arabidopsis (Huang animal system will be drawn in which much more is known about et al., 2002; Polverari et al., 2003). Promoter analysis of the genes the effect of S-nitrosylation on transcription. co-expressed after NO treatment revealed the accumulation of cer- tain transcription factor binding sites, like octopine synthase gene S-NITROSYLATED NUCLEAR PROTEINS (ocs) elements and WRKY-sites (Palmieri et al., 2008). This raised GLYCERALDEHYDE 3-PHOSPHATE DEHYDROGENASE AND CYTOSOLIC the question whether NO affects transcription directly by nitro- ALDOLASE sylating transcription factors or other transcriptional regulators. It is well-known that glyceraldehyde 3-phosphate dehydrogenase In some bacteria, for instance, redox-sensitive cysteine residues of (GAPDH) not only plays an important role in glycolysis but also the transcriptional activator OxyR can undergo redox-dependent participates in nuclear events like regulation of gene transcription, FIGURE 1 | S-nitrosylation can affect gene transcription in several 2007; Lindermayr et al., 2010; Sha and Marshall, 2012). Additionally, ways. Upon S-nitrosylation proteins can change their subcellular localization SNO-formation can lead to association/dissociation of macromolecular which