title: 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.
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.
authors: State Key Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Peking-Tsinghua Center for Life Sciences, Beijing 100871, China.
authors: Wenrong
authors: W
authors: He
authors: Javier
authors: J
authors: Brumos
authors: Hongjiang
authors: H
authors: Li
authors: Yusi
authors: Y
authors: Ji
authors: Meng
authors: M
authors: Ke
authors: Xinqi
authors: X
authors: Gong
authors: Qinglong
authors: Q
authors: Zeng
authors: Wenyang
authors: W
authors: Li
authors: Xinyan
authors: X
authors: Zhang
authors: Fengying
authors: F
authors: An
authors: Xing
authors: X
authors: Wen
authors: Pengpeng
authors: P
authors: Li
authors: Jinfang
authors: J
authors: Chu
authors: Xiaohong
authors: X
authors: Sun
authors: Cunyu
authors: C
authors: Yan
authors: Nieng
authors: N
authors: Yan
authors: De-Yu
authors: DY
authors: Xie
authors: Natasha
authors: N
authors: Raikhel
authors: Zhenbiao
authors: Z
authors: Yang
authors: Anna N
authors: AN
authors: Stepanova
authors: Jose M
authors: JM
authors: Alonso
authors: Hongwei
authors: H
authors: Guo
mesh_terms: D017360:Arabidopsis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005030:Ethylenes / Q000378:metabolism* / Q000494:pharmacology; D044783:F-Box Proteins / Q000378:metabolism; D007210:Indoleacetic Acids / Q000378:metabolism* / Q000494:pharmacology; D007737:Kynurenine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000378:metabolism; D018517:Plant Roots / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D054852:Small Molecule Libraries; D014157:Transcription Factors / Q000378:metabolism; D051279:Tryptophan Transaminase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D029681:Arabidopsis Proteins; D004268:DNA-Binding Proteins; C481045:EBF2 protein, Arabidopsis; C106987:EIN3 protein, Arabidopsis; D004791:Enzyme Inhibitors; D005030:Ethylenes; D044783:F-Box Proteins; D007210:Indoleacetic Acids; D009687:Nuclear Proteins; D054852:Small Molecule Libraries; D014157:Transcription Factors; D007737:Kynurenine; C030737:indoleacetic acid; C036216:ethylene; D051279:Tryptophan Transaminase