Maintaining nitric oxide (NO) homeostasis is essential for normal plant physiological processes. However, very little is known about the mechanisms of NO modulation in plants. Here, we report a unique mechanism for the catabolism of NO based on the reaction with the plant hormone cytokinin. We screened for NO-insensitive mutants in Arabidopsis and isolated two allelic lines, cnu1-1 and 1-2 (continuous NO-unstressed 1), that were identified as the previously reported altered meristem program 1 (amp1) and as having elevated levels of cytokinins. A double mutant of cnu1-2 and nitric oxide overexpression 1 (nox1) reduced the severity of the phenotypes ascribed to excess NO levels as did treating the nox1 line with trans-zeatin, the predominant form of cytokinin in Arabidopsis. We further showed that peroxinitrite, an active NO derivative, can react with zeatin in vitro, which together with the results in vivo suggests that cytokinins suppress the action of NO most likely through direct interaction between them, leading to the reduction of endogenous NO levels. These results provide insights into NO signaling and regulation of its bioactivity in plants.is one of the most widespread signaling molecules in living organisms (1, 2). In plants, NO is involved in the regulation of numerous physiological processes during growth and development and is also an important modulator of disease resistance (2-4). Several laboratories discovered that NO is produced not only from nitrate/nitrite but also from L-arginine (L-Arg), which is the main substrate for NO synthesis in animals (4-6). NO is also a widespread atmospheric pollutant. Therefore, this gas not only is a pivotal player in signal transduction but also has the potential to exert significant deleterious effects by being a pollutant. As an inevitable result, increased NO levels in the atmosphere can influence multiple NO-regulated processes in organisms. Despite the wealth of information gathered from analyses of NO functioning in plants, the molecular processes underlying NO effects in plants are still largely unknown.NO differs from other signaling molecules by being reactive, lipophilic, and volatile. In fact, chemically, NO is a free radical, and such a reactive molecule is unlikely to interact specifically with a single specific receptor (3). In animals, NO appears to act through the chemical modification of targets. NO can bind to transition metals of metalloproteins (metal nitrosylation). It also can bind covalently to cysteine (S-nitrosylation) and tyrosine (tyrosine nitration) residues (3,7,8). Such specific protein modifications are emerging as key mechanistic intermediates for NO signal transduction. In plant cells, NO has also been found to regulate the activity of various target proteins through S-or metal-nitrosylation and probably through tyrosine nitration as well (9-13).Furthermore, it has been shown that NO takes part in different phytohormone signaling pathways, frequently under the control of hormonal stimuli. For instance, NO functions in auxin-induc...