RT Journal Article SR Electronic T1 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 JF The Plant Cell JO Plant Cell FD American Society of Plant Biologists SP 3944 OP 3960 DO 10.1105/tpc.111.089029 VO 23 IS 11 A1 He, Wenrong A1 Brumos, Javier A1 Li, Hongjiang A1 Ji, Yusi A1 Ke, Meng A1 Gong, Xinqi A1 Zeng, Qinglong A1 Li, Wenyang A1 Zhang, Xinyan A1 An, Fengying A1 Wen, Xing A1 Li, Pengpeng A1 Chu, Jinfang A1 Sun, Xiaohong A1 Yan, Cunyu A1 Yan, Nieng A1 Xie, De-Yu A1 Raikhel, Natasha A1 Yang, Zhenbiao A1 Stepanova, Anna N. A1 Alonso, Jose M. A1 Guo, Hongwei YR 2011 UL http://www.plantcell.org/content/23/11/3944.abstract AB 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.