Non-specific effects of a CINNAMATE-4-HYDROXYLASE inhibitor on auxin homeostasis

生长素 生物化学 内生 化学 分解代谢抑制 生物 细胞生物学 基因 突变体
作者
Ilias El Houari,Petr Klíma,Alexandra Baekelandt,Paul Staswick,Veselina Uzunova,Charo I. del Genio,Ward Steenackers,Petre I. Dobrev,Ondřej Novák,Richard Napier,Jan Petrášek,Dirk Inzé,Wout Boerjan,Bartel Vanholme
标识
DOI:10.1101/2021.10.27.466161
摘要

ABSTRACT Chemical inhibitors are often implemented for the functional characterization of genes to overcome the limitations associated with genetic approaches. Although being a powerful tool, off-target effects of these inhibitors are easily overlooked in a complex biological setting. Here we illustrate the implications of such secondary effects by focusing on piperonylic acid (PA), an inhibitor of CINNAMATE-4-HYDROXYLASE (C4H) that is often 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 auxin catabolite indole-3-acetic acid (IAA)-Asp. By competing for the same enzyme, PA interferes with auxin conjugation, resulting in an increase in cellular auxin concentrations. These increased auxin levels likely further contribute to an increase in adventitious rooting previously observed upon PA-treatment. Despite the focus on GH3.6 in this report, PA is conjugated by an array of enzymes and their subsequent reduced activity on native substrates could potentially affect a whole set of physiological processes in the plant. We conclude that surrogate occupation of the endogenous conjugation machinery in the plant by exogenous compounds is likely a more general phenomenon that is rarely considered in pharmacological studies. Our results hereby provide an important basis for future reference in studies using chemical inhibitors.
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