PUBLICATION

The Small Molecule R-(-)-β-O-Methylsynephrine Binds to Nucleoporin 153 kDa and Inhibits Angiogenesis

Authors
Kim, N.H., Pham, N.B., Quinn, R.J., Shim, J.S., Cho, H., Cho, S.M., Park, S.W., Kim, J.H., Seok, S.H., Oh, J.W., Kwon, H.J.
ID
ZDB-PUB-150730-2
Date
2015
Source
International journal of biological sciences   11: 1088-99 (Journal)
Registered Authors
Keywords
Angiogenesis, NUP153, Natural product, Small molecule, Target identification
MeSH Terms
  • Animals
  • Mice
  • Neovascularization, Pathologic/metabolism*
  • Nuclear Proteins/metabolism*
  • Protein Binding/genetics
  • Protein Binding/physiology
  • Synephrine/analogs & derivatives*
  • Synephrine/metabolism
  • Zebrafish
PubMed
26221075 Full text @ Int. J. Biol. Sci.
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping