title: Amine oxidase copper-containing 1 (AOC1) is a downstream target gene of the Wilms tumor protein, WT1, during kidney development.
abstract: Amine oxidase copper-containing 1 (AOC1; formerly known as amiloride-binding protein 1) is a secreted glycoprotein that catalyzes the degradation of putrescine and histamine. Polyamines and their diamine precursor putrescine are ubiquitous to all organisms and fulfill pivotal functions in cell growth and proliferation. Despite the importance of AOC1 in regulating polyamine breakdown, very little is known about the molecular mechanisms that control its expression. We report here that the Wilms tumor protein, WT1, which is necessary for normal kidney development, activates transcription of the AOC1 gene. Expression of a firefly luciferase reporter under control of the proximal AOC1 promoter was significantly enhanced by co-transfection of a WT1 expression construct. Binding of WT1 protein to a cis-regulatory element in the AOC1 promoter was confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Antisense inhibition of WT1 protein translation strongly reduced Aoc1 transcripts in cultured murine embryonic kidneys and gonads. Aoc1 mRNA levels correlated with WT1 protein in several cell lines. Double immunofluorescent staining revealed a co-expression of WT1 and AOC1 proteins in the developing genitourinary system of mice and rats. Strikingly, induced changes in polyamine homeostasis affected branching morphogenesis of cultured murine embryonic kidneys in a developmental stage-specific manner. These findings suggest that WT1-dependent control of polyamine breakdown, which is mediated by changes in AOC1 expression, has a role in kidney organogenesis.
authors.affiliation: From the Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Kirschner
authors.affiliation: From the Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Julian F W
authors.initials: JF
authors.lastname: Braun
authors.affiliation: From the Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Charlotte L
authors.initials: CL
authors.lastname: Jacobi
authors.affiliation: From the Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Rudigier
authors.affiliation: From the Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Anja Bondke
authors.initials: AB
authors.lastname: Persson
authors.affiliation: From the Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany holger.scholz@charite.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Scholz
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D055785:Gene Knockdown Techniques; D006066:Gonads / Q000196:embryology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D025721:WT1 Proteins; D006631:Amine Oxidase (Copper-Containing)
keywords: Development; Gene Expression; Polyamine; Transcription Regulation; Tumor Suppressor Gene