@article{3a9b1095931d48b5beb09f72566b491e,
title = "Chemical inhibition of the auxin inactivation pathway uncovers the roles of metabolic turnover in auxin homeostasis",
abstract = "The phytohormone auxin, indole-3-acetic acid (IAA), plays a prominent role in plant development. Auxin homeostasis is coordinately regulated by auxin synthesis, transport, and inactivation; however, the physiological contribution of auxin inactivation to auxin homeostasis has not been determined. The GH3 IAA-amino acid conjugating enzymes play a central role in auxin inactivation. Chemical inhibition of GH3 proteins in planta is challenging because the inhibition of these enzymes leads to IAA overaccumulation that rapidly induces GH3 expression. Here, we report the characterization of a potent GH3 inhibitor, kakeimide, that selectively targets IAA-conjugating GH3 proteins. Chemical knockdown of the auxin inactivation pathway demonstrates that auxin turnover is very rapid (about 10 min) and indicates that both auxin biosynthesis and inactivation dynamically regulate auxin homeostasis.",
keywords = "auxin, chemical biology, plant hormone",
author = "Kosuke Fukui and Kazushi Arai and Yuka Tanaka and Yuki Aoi and Vandna Kukshal and Jez, {Joseph M.} and Kubes, {Martin F.} and Richard Napier and Yunde Zhao and Hiroyuki Kasahara and Hayashi, {Ken Ichiro}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Dr. Roberto Solano (Universidad Aut{\'o}noma de Madrid) and Prof. Minoru Ueda and Dr. Yousuke Takaoka (Tohoku University) for providing the mutant seeds and helpful comments. We thank the members of the K.-i.H. and H.K. laboratories for assistance in the measurement of HPLC, LC-MS/MS, and phenotypic data. This work was supported by grants from the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (19K15761 to K.F.; 19H03253 and 21K19097 to K.-i.H.; 21H02501 to H.K.) and Grant for Promotion of Okayama Univ. of Science (OUS) Research Project (OUS-RP-21-4 to K.-i.H.). M.F.K. and R.N. acknowledge the grant from Hrizon 2020 (H2020-MSCA-IF-2017-792329) and equipment access at the Warwick Integrative Synthetic Biology Centre which is funded by BB/M017982/1. J.M.J. acknowledges the grant from the NSF (MCB-1614539). Publisher Copyright: {\textcopyright} 2022 the Author(s).",
year = "2022",
month = aug,
day = "9",
doi = "10.1073/pnas.2206869119",
language = "English",
volume = "119",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "32",
}