title: The Small Molecule R-(-)-β-O-Methylsynephrine Binds to Nucleoporin 153 kDa and Inhibits Angiogenesis.
abstract: R-(-)-β-O-methylsynephrine (OMe-Syn) is a naturally occurring small molecule that was identified in a previous screen as an inhibitor of angiogenesis. In this study, we conducted two animal model experiments to investigate the in vivo antiangiogenic activity of OMe-Syn. OMe-Syn significantly inhibited angiogenesis in a transgenic zebrafish model as well as in a mouse retinopathy model. To elucidate the underlying mechanisms responsible for the antiangiogenic activity of OMe-Syn, we used phage display cloning to isolate potential OMe-Syn binding proteins from human cDNA libraries and identified nucleoporin 153 kDa (NUP153) as a primary binding partner of OMe-Syn. OMe-Syn competitively inhibited mRNA binding to the RNA-binding domain of NUP153. Furthermore, depletion of NUP153 in human cells or zebrafish embryos led to an inhibition of angiogenesis, in a manner similar to that seen in response to OMe-Syn treatment. These data suggest that OMe-Syn is a promising candidate for the development of a novel antiangiogenic agent and that inhibition of NUP153 is possibly responsible for the antiangiogenic activity of OMe-Syn.
authors.affiliation: 1. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Kim
authors.affiliation: 2. Eskitis Institute, Griffith University, Brisbane QLD 4111, Australia.
authors.forename: Ngoc Bich
authors.initials: NB
authors.lastname: Pham
authors.affiliation: 2. Eskitis Institute, Griffith University, Brisbane QLD 4111, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.affiliation: 3. Faculty of Health Sciences, University of Macau, Av. Universidade, Taipa, Macau SAR, China.
authors.forename: Joong Sup
authors.initials: JS
authors.lastname: Shim
authors.affiliation: 1. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Cho
authors.affiliation: 1. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Cho
authors.affiliation: 4. Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Park
authors.affiliation: 4. Department of Ophthalmology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 5. Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Seok
authors.affiliation: 1. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Oh
authors.affiliation: 1. Department of Biotechnology, Translational Research Center for Protein Function Control, College of Life Science & Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea ; 6. Department of Internal Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D000818:Animals; D004809:Ephedrine / Q000031:analogs & derivatives; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D013578:Synephrine / Q000031:analogs & derivatives* / Q000378:metabolism; D015027:Zebrafish
chemical_list: D009687:Nuclear Proteins; C026055:oxilofrine; D004809:Ephedrine; D013578:Synephrine
keywords: Angiogenesis; NUP153; Natural product; Small molecule; Target identification