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Bestatin, a potent inhibitor of some aminopeptidases, was shown previously to be a powerful inducer of wound-response genes in tomato (Lycopersicon esculentum). Here, we present several lines of evidence showing that bestatin specifically activates jasmonic acid (JA) signaling in plants. First, bestatin specifically activates the expression of JA-inducible genes in tomato and Arabidopsis (Arabidopsis thaliana). Second, the induction of JA-responsive genes by bestatin requires the COI1-dependent JA-signaling pathway, but does not depend strictly on JA biosynthesis. Third, microarray analysis using Arabidopsis whole-genome chip demonstrates that the gene expression profile of bestatin-treated plants is similar to that of JA-treated plants. Fourth, bestatin promotes a series of JA-related developmental phenotypes. Taken together, the unique action mode of bestatin in regulating JA-signaled processes leads us to the hypothesis that bestatin exerts its effects through the modulation of some key regulators in JA signaling. We have employed bestatin as an experimental tool to dissect JA signaling through a chemical genetic screening, which yielded a collection of Arabidopsis bestatin-resistant (ber) mutants that are insensitive to the inhibitory effects of bestatin on root elongation. Further characterization efforts demonstrate that some ber mutants are defective in various JA-induced responses, which allowed us to classify the ber mutants into three phenotypic groups: JA-insensitive ber mutants, JA-hypersensitive ber mutants, and mutants insensitive to bestatin but showing normal response to JA. Genetic and phenotypic analyses of the ber mutants with altered JA responses indicate that we have identified several novel loci involved in JA signaling.

Bestatin, an Inhibitor of Aminopeptidases, Provides a Chemical Genetics Approach to Dissect Jasmonate Signaling in Arabidopsis