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Non‐specific effects of the CINNAMATE‐4‐HYDROXYLASE inhibitor piperonylic acid
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El Houari, Ilias, Klíma, Petr, Baekelandt, Alexandra, Staswick, Paul E., Uzunova, Veselina, Del Genio, Charo I., Steenackers, Ward, Dobrev, Petre I., Filepová, Roberta, Novák, Ondrej, Napier, Richard, Petrášek, Jan, Inzé, Dirk, Boerjan, Wout and Vanholme, Bartel (2023) Non‐specific effects of the CINNAMATE‐4‐HYDROXYLASE inhibitor piperonylic acid. The Plant Journal, 115 (2). pp. 470-479. doi:10.1111/tpj.16237 ISSN 0960-7412.
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Official URL: http://doi.org/10.1111/tpj.16237
Abstract
Chemical inhibitors are often implemented for the functional characterization of genes to overcome the limitations associated with genetic approaches. Although it is well established that the specificity of the compound is key to success of a pharmacological approach, off-target effects are often overlooked or simply neglected in a complex biological setting. Here we illustrate the cause and implications of such secondary effects by focusing on piperonylic acid (PA), an inhibitor of CINNAMATE-4-HYDROXYLASE (C4H) that is frequently used to investigate the involvement of lignin during plant growth and development. When supplied to plants, we found that PA is recognized as a substrate by GRETCHEN HAGEN 3.6 (GH3.6), an amido synthetase involved in the formation of the indole-3-acetic acid (IAA) conjugate IAA-Asp. By competing for the same enzyme, PA interferes with IAA conjugation, resulting in an increase in IAA concentrations in the plant. In line with the broad substrate specificity of the GH3 family of enzymes, treatment with PA increased not only IAA levels but also those of other GH3-conjugated phytohormones, namely jasmonic and salicylic acid. Finally, we found that interference with the endogenous function of GH3s potentially contributes to phenotypes previously observed upon PA-treatment. We conclude that deregulation of phytohormone homeostasis by surrogate occupation of the conjugation machinery in the plant is likely a general phenomenon when using chemical inhibitors. Our results hereby provide a novel and important basis for future reference in studies using chemical inhibitors.
Item Type: | Journal Article | |||||||||||||||||||||||||||||||||
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Subjects: | Q Science > QD Chemistry Q Science > QK Botany |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Chemical inhibitors | |||||||||||||||||||||||||||||||||
Journal or Publication Title: | The Plant Journal | |||||||||||||||||||||||||||||||||
Publisher: | Wiley-Blackwell Publishing Ltd. | |||||||||||||||||||||||||||||||||
ISSN: | 0960-7412 | |||||||||||||||||||||||||||||||||
Official Date: | July 2023 | |||||||||||||||||||||||||||||||||
Dates: |
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Volume: | 115 | |||||||||||||||||||||||||||||||||
Number: | 2 | |||||||||||||||||||||||||||||||||
Page Range: | pp. 470-479 | |||||||||||||||||||||||||||||||||
DOI: | 10.1111/tpj.16237 | |||||||||||||||||||||||||||||||||
Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||
Publication Status: | Published | |||||||||||||||||||||||||||||||||
Re-use Statement: | This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at http://doi.org/10.1111/tpj.16237. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited | |||||||||||||||||||||||||||||||||
Access rights to Published version: | Restricted or Subscription Access | |||||||||||||||||||||||||||||||||
Date of first compliant deposit: | 13 April 2023 | |||||||||||||||||||||||||||||||||
Date of first compliant Open Access: | 10 April 2024 | |||||||||||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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