title: Identification of an ABCB/P-glycoprotein-specific inhibitor of auxin transport by chemical genomics.
abstract: Plant development and physiology are widely determined by the polar transport of the signaling molecule auxin. This process is controlled on the cellular efflux level catalyzed by members of the PIN (pin-formed) and ABCB (ATP-binding cassette protein subfamily B)/P-glycoprotein family that can function independently and coordinately. In this study, we have identified by means of chemical genomics a novel auxin transport inhibitor (ATI), BUM (2-[4-(diethylamino)-2-hydroxybenzoyl]benzoic acid), that efficiently blocks auxin-regulated plant physiology and development. In many respects, BUM resembles the functionality of the diagnostic ATI, 1-N-naphtylphtalamic acid (NPA), but it has an IC(50) value that is roughly a factor 30 lower. Physiological analysis and binding assays identified ABCBs, primarily ABCB1, as key targets of BUM and NPA, whereas PIN proteins are apparently not directly affected. BUM is complementary to NPA by having distinct ABCB target spectra and impacts on basipetal polar auxin transport in the shoot and root. In comparison with the recently identified ATI, gravacin, it lacks interference with ABCB membrane trafficking. Individual modes or targets of action compared with NPA are reflected by apically shifted root influx maxima that might be the result of altered BUM binding preferences or affinities to the ABCB nucleotide binding folds. This qualifies BUM as a valuable tool for auxin research, allowing differentiation between ABCB- and PIN-mediated efflux systems. Besides its obvious application as a powerful weed herbicide, BUM is a bona fide human ABCB inhibitor with the potential to restrict multidrug resistance during chemotherapy.
authors.affiliation: Laboratory of Plant Systems Bio-Dynamics, Pohang University of Science and Technology, 790-784 Pohang, Korea.
authors.forename: Jun-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Sina
authors.initials: S
authors.lastname: Henrichs
authors.forename: Aurélien
authors.initials: A
authors.lastname: Bailly
authors.forename: Vincent
authors.initials: V
authors.lastname: Vincenzetti
authors.forename: Valpuri
authors.initials: V
authors.lastname: Sovero
authors.forename: Stefano
authors.initials: S
authors.lastname: Mancuso
authors.forename: Stephan
authors.initials: S
authors.lastname: Pollmann
authors.forename: Daehwang
authors.initials: D
authors.lastname: Kim
authors.forename: Markus
authors.initials: M
authors.lastname: Geisler
authors.forename: Hong-Gil
authors.initials: HG
authors.lastname: Nam
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism*; D017360:Arabidopsis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D019817:Benzoic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D018506:Gene Expression Regulation, Plant / Q000187:drug effects; D023281:Genomics; D007210:Indoleacetic Acids / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013379:Substrate Specificity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007210:Indoleacetic Acids; D054852:Small Molecule Libraries; D019817:Benzoic Acid
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