Yokonolide B, a Novel Inhibitor of Auxin Action, Blocks Degradation of AUX/IAA Factors

• Published in: The Journal of biological chemistry 2003-06, Vol.278 (26), p.23797-23806
• Main Authors: Hayashi, Ken-ichiro, Jones, Alan M, Ogino, Kentaro, Yamazoe, Atsushi, Oono, Yutaka, Inoguchi, Masahiko, Kondo, Hirokiyo, Nozaki, Hiroshi
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Arabidopsis - genetics; Cell Division - drug effects; Gene Expression Profiling; Gene Expression Regulation - drug effects; Genes, Plant - drug effects; Indoleacetic Acids - antagonists & inhibitors; Indoleacetic Acids - genetics; Indoleacetic Acids - physiology; Macrolides; Plant Growth Regulators - antagonists & inhibitors; Promoter Regions, Genetic; Repressor Proteins - drug effects; Repressor Proteins - metabolism; Signal Transduction; Spiro Compounds - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M300299200

Yokonolide B (YkB; also known as A82548A), a spiroketal-macrolide, was isolated from Streptomyces diastatochromogenes B59 in a screen for inhibitors of β-glucoronidase expression under the control of an auxin-responsive promoter in Arabidopsis . YkB inhibits the expression of auxin-inducible genes as shown using native and synthetic auxin promoters as well as using expression profiling of 8,300 Arabidopsis gene probes but does not affect expression of an abscisic acid- and a gibberellin A 3 -inducible gene. The mechanism of action of YkB is to block AUX/IAA protein degradation; however, YkB is not a general proteasome inhibitor. YkB blocks auxin-dependent cell division and auxin-regulated epinastic growth mediated by auxin-binding protein 1. Gain of function mutants such as shy2 - 2, slr1 , and axr2 - 1 encoding AUX/IAA transcriptional repressors and loss of function mutants encoding components of the ubiquitin-proteolytic pathway such as axr1 - 3 and tir1 - 1 , which display increased AUX/IAAs protein stability, are less sensitive to YkB, although axr1 and tir1 mutants were sensitive to MG132, a general proteasome inhibitor, consistent with a site of action downstream of AXR1 and TIR. YkB-treated seedlings displayed similar phenotypes as dominant AUX/IAA mutants. Taken together, these results indicate that YkB acts to block AUX/IAA protein degradation upstream of AXR and TIR, links a shared element upstream of AUX/IAA protein stability to auxin-induced cell division/elongation and to auxin-binding protein 1, and provides a new tool to dissect auxin signal transduction.