title: Substituted Phthalimide AC94377 Is a Selective Agonist of the Gibberellin Receptor GID1.
abstract: Gibberellin (GA) is a major plant hormone that regulates plant growth and development and is widely used as a plant growth regulator in agricultural production. There is an increasing demand for function-limited GA mimics due to the limitations on the agronomical application of GA to crops, including GA's high cost of producing and its leading to the crops' lodging. AC94377, a substituted phthalimide, is a chemical that mimics the growth-regulating activity of GAs in various plants, despite its structural difference. Although AC94377 is widely studied in many weeds and crops, its mode of action as a GA mimic is largely unknown. In this study, we confirmed that AC94377 displays GA-like activities in Arabidopsis (Arabidopsis thaliana) and demonstrated that AC94377 binds to the Arabidopsis GIBBERELLIN INSENSITIVE DWARF1 (GID1) receptor (AtGID1), forms the AtGID1-AC94377-DELLA complex, and induces the degradation of DELLA protein. Our results also indicated that AC94377 is selective for a specific subtype among three AtGID1s and that the selectivity of AC94377 is attributable to a single residue at the entrance to the hydrophobic pocket of GID1. We conclude that AC94377 is a GID1 agonist with selectivity for a specific subtype of GID1, which could be further developed and used as a function-limited regulator of plant growth in both basic study and agriculture.
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Kai
authors.identifier: 0000-0001-9901-5293
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Masato
authors.initials: M
authors.lastname: Otani
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimotakahara
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Yoon
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Tomoko
authors.initials: T
authors.lastname: Miyaji
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakano
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.).|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.).|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.).
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nakajima
authors.affiliation: Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (K.J., M.O., H.S., J.-M.Y., S.-H.P., H.N., M.N., T.A.); asami@mail.ecc.u-tokyo.ac.jp.|Gene Discovery Research Group, Center for Sustainable Resource Science, RIKEN, Wako, Saitama 351-0198, Japan (T.M., T.N.); asami@mail.ecc.u-tokyo.ac.jp.|Department of Biochemistry, King Abdulaziz University, Jeddah 21589, Saudi Arabia (T.A.); and asami@mail.ecc.u-tokyo.ac.jp.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan (T.A.) asami@mail.ecc.u-tokyo.ac.jp.
authors.forename: Tadao
authors.identifier: 0000-0003-0774-6203
authors.initials: T
authors.lastname: Asami
mesh_terms: D017360:Arabidopsis / Q000187:drug effects* / Q000378:metabolism; D029681:Arabidopsis Proteins / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018525:Germination / Q000187:drug effects; D005875:Gibberellins / Q000378:metabolism; D018546:Hypocotyl / Q000187:drug effects; D010797:Phthalimides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D030821:Plants, Genetically Modified; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014026:Nicotiana / Q000235:genetics
chemical_list: C000625001:AC94377; D029681:Arabidopsis Proteins; C109555:GAI protein, Arabidopsis; C512225:GID1a protein, Arabidopsis; D005875:Gibberellins; D010797:Phthalimides; D011956:Receptors, Cell Surface