title: Yokonolide B, a novel inhibitor of auxin action, blocks degradation of AUX/IAA factors.
abstract: Yokonolide B (YkB; also known as A82548A), a spiroketal-macrolide, was isolated from Streptomyces diastatochromogenes B59 in a screen for inhibitors of beta-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 8300 Arabidopsis gene probes but does not affect expression of an abscisic acid- and a gibberellin A3-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.
authors.affiliation: Department of Biochemistry, Okayama University of Science, 1-1 Ridai-cho, Okayama 700-0005, Japan. hayashi@dbc.ous.ac.jp
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Alan M
authors.initials: AM
authors.lastname: Jones
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ogino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamazoe
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oono
authors.forename: Masahiko
authors.initials: M
authors.lastname: Inoguchi
authors.forename: Hirokiyo
authors.initials: H
authors.lastname: Kondo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nozaki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017360:Arabidopsis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D017343:Genes, Plant / Q000187:drug effects; D007210:Indoleacetic Acids / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D018942:Macrolides; D010937:Plant Growth Regulators / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: C096633:A 82548A; D000900:Anti-Bacterial Agents; D007210:Indoleacetic Acids; D018942:Macrolides; D010937:Plant Growth Regulators; D012097:Repressor Proteins; D013141:Spiro Compounds