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.
Citation
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. (2015) The Small Molecule R-(-)-β-O-Methylsynephrine Binds to Nucleoporin 153 kDa and Inhibits Angiogenesis. International journal of biological sciences. 11:1088-99.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping