title: JunB is required for endothelial cell morphogenesis by regulating core-binding factor beta.
abstract: The molecular mechanism triggering the organization of endothelial cells (ECs) in multicellular tubules is mechanistically still poorly understood. We demonstrate that cell-autonomous endothelial functions of the AP-1 subunit JunB are required for proper endothelial morphogenesis both in vivo in mouse embryos with endothelial-specific ablation of JunB and in in vitro angiogenesis models. By cDNA microarray analysis, we identified core-binding factor beta (CBFbeta), which together with the Runx proteins forms the heterodimeric core-binding transcription complex CBF, as a novel JunB target gene. In line with our findings, expression of the CBF target MMP-13 was impaired in JunB-deficient ECs. Reintroduction of CBFbeta into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFbeta in EC morphogenesis.
authors.affiliation: Division of Signal Transduction and Growth Control, German Cancer Research Center, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Licht
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Pein
authors.forename: Lore
authors.initials: L
authors.lastname: Florin
authors.forename: Bettina
authors.initials: B
authors.lastname: Hartenstein
authors.forename: Hendrik
authors.initials: H
authors.lastname: Reuter
authors.forename: Bernd
authors.initials: B
authors.lastname: Arnold
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
authors.forename: Marina
authors.initials: M
authors.lastname: Schorpp-Kistner
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D015153:Blotting, Western; D015687:Cell Hypoxia; D002465:Cell Movement; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D024043:Collagen Type II / Q000235:genetics / Q000502:physiology; D050657:Core Binding Factor alpha Subunits / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D019426:Integrases / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D024043:Collagen Type II; D050657:Core Binding Factor alpha Subunits; D050658:Core Binding Factor beta Subunit; D016755:Proto-Oncogene Proteins c-jun; C045073:Cre recombinase; D019426:Integrases; D053509:Matrix Metalloproteinase 13