A small-molecule screen identifies L-kynurenine as a competitive inhibitor of TAA1/TAR activity in ethylene-directed auxin biosynthesis and root growth in Arabidopsis.

TitleA small-molecule screen identifies L-kynurenine as a competitive inhibitor of TAA1/TAR activity in ethylene-directed auxin biosynthesis and root growth in Arabidopsis.
Publication TypeJournal Article
Year of Publication2011
AuthorsHe, W, Brumos, J, Li, H, Ji, Y, Ke, M, Gong, X, Zeng, Q, Li, W, Zhang, X, An, F, Wen, X, Li, P, Chu, J, Sun, X, Yan, C, Yan, N, Xie, D-Y, Raikhel, N, Yang, Z, Stepanova, AN, Alonso, JM, Guo, H
JournalPlant Cell
Volume23
Issue11
Pagination3944-60
Date Published2011 Nov
ISSN1532-298X
KeywordsArabidopsis, Arabidopsis Proteins, Cell Nucleus, Enzyme Inhibitors, Ethylenes, F-Box Proteins, Indoleacetic Acids, Kynurenine, Models, Molecular, Nuclear Proteins, Plant Roots, Small Molecule Libraries, Transcription Factors, Tryptophan Transaminase
Abstract

The interactions between phytohormones are crucial for plants to adapt to complex environmental changes. One example is the ethylene-regulated local auxin biosynthesis in roots, which partly contributes to ethylene-directed root development and gravitropism. Using a chemical biology approach, we identified a small molecule, l-kynurenine (Kyn), which effectively inhibited ethylene responses in Arabidopsis thaliana root tissues. Kyn application repressed nuclear accumulation of the ETHYLENE INSENSITIVE3 (EIN3) transcription factor. Moreover, Kyn application decreased ethylene-induced auxin biosynthesis in roots, and TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS1/TRYPTOPHAN AMINOTRANSFERASE RELATEDs (TAA1/TARs), the key enzymes in the indole-3-pyruvic acid pathway of auxin biosynthesis, were identified as the molecular targets of Kyn. Further biochemical and phenotypic analyses revealed that Kyn, being an alternate substrate, competitively inhibits TAA1/TAR activity, and Kyn treatment mimicked the loss of TAA1/TAR functions. Molecular modeling and sequence alignments suggested that Kyn effectively and selectively binds to the substrate pocket of TAA1/TAR proteins but not those of other families of aminotransferases. To elucidate the destabilizing effect of Kyn on EIN3, we further found that auxin enhanced EIN3 nuclear accumulation in an EIN3 BINDING F-BOX PROTEIN1 (EBF1)/EBF2-dependent manner, suggesting the existence of a positive feedback loop between auxin biosynthesis and ethylene signaling. Thus, our study not only reveals a new level of interactions between ethylene and auxin pathways but also offers an efficient method to explore and exploit TAA1/TAR-dependent auxin biosynthesis.

DOI10.1105/tpc.111.089029
Alternate JournalPlant Cell
PubMed ID22108404
PubMed Central IDPMC3246337
Grant ListR01 GM081451 / GM / NIGMS NIH HHS / United States
GM081451 / GM / NIGMS NIH HHS / United States
GM081451-03S2 / GM / NIGMS NIH HHS / United States