title: FIH-1, a novel interactor of mindbomb, functions as an essential anti-angiogenic factor during zebrafish vascular development.
abstract: OBJECTIVE
  It has been shown that Mindbomb (Mib), an E3 Ubiquitin ligase, is an essential modulator of Notch signaling during development. However, its effects on vascular development remain largely unknown.
  
  
  RESULTS
  We identified a number of novel proteins that physically interact with Mib, including the Factor Inhibiting Hypoxia Inducible Factor 1 (FIH-1, also known as HIF1AN) from a yeast two hybrid screen, as previously reported. In cultured cells, FIH-1 colocalizes with Mib1, corroborating their potential interaction. In zebrafish embryos, FIH-1 appears to modulate VEGF-A signaling activity; depletion of fih-1 induces ectopic expression of vascular endothelial growth factor-a (vegfa) and leads to exuberant ectopic sprouts from intersegmental vessels (ISVs). Conversely, over-expression of fih-1 substantially attenuates the formation of ISVs, which can be rescued by concurrent over-expression of vegfa, indicating that FIH-1/HIF1AN may fine tune VEGF-A signaling.
  
  
  CONCLUSIONS
  Taken together, our data suggest that FIH-1 interacts with Mib E3 Ubiquitin ligase and modulates vascular development by attenuating VEGF-A signaling activity.
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Korea; Department of Developmental Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ju-Hoon
authors.initials: JH
authors.lastname: So
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Jun-Dae
authors.initials: JD
authors.lastname: Kim
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Korea.
authors.forename: Kyeong-Won
authors.initials: KW
authors.lastname: Yoo
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Korea.
authors.forename: Hyun-Taek
authors.initials: HT
authors.lastname: Kim
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Korea.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America; School of Biological Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Suk-Won
authors.initials: SW
authors.lastname: Jin
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Kim
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D015870:Gene Expression; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism* / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011485:Protein Binding; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015027:Zebrafish
chemical_list: D043925:Angiogenesis Inducing Agents; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D044767:Ubiquitin-Protein Ligases