Homeoprotein Msx1-PIASy interaction inhibits angiogenesis

Cited 1 time in scopus
Metadata Downloads
Title
Homeoprotein Msx1-PIASy interaction inhibits angiogenesis
Author(s)
Myung Jin Son; S B Rho; K Kim; M Oh; C Son; S Y Song; K Park
Bibliographic Citation
Cells, vol. 9, no. 8, pp. 1854-1854
Publication Year
2020
Abstract
Previously, we demonstrated that the homeoprotein Msx1 interaction with p53 inhibited tumor growth by inducing apoptosis. However, Msx1 can exert its tumor suppressive effect through the inhibition of angiogenesis since growth of the tumor relies on sufficient blood supply from the existing vessels to provide oxygen and nutrients for tumor growth. We hypothesized that the inhibition of tumor growth by Msx1 might be due to the inhibition of angiogenesis. Here, we explored the role of Msx1 in angiogenesis. Overexpression of Msx1 in HUVECs inhibited angiogenesis, and silencing of Msx1 by siRNA abrogated its anti-angiogenic effects. Furthermore, forced expression of Msx1 in mouse muscle tissue inhibited vessel sprouting, and application of an Ad-Msx1-transfected conditioned medium onto the chicken chorioallantoic membrane (CAM) led to a significant inhibition of new vessel formation. To explore the underlying mechanism of Msx1-mediated angiogenesis, yeast two-hybrid screening was performed, and we identified PIASy (protein inhibitor of activated STAT Y) as a novel Msx1-interacting protein. We mapped the homeodomain of Msx1 and the C-terminal domain of PIASy as respective interacting domains. Consistent with its anti-angiogenic function, overexpression of Msx1 suppressed the reporter activity of VEGF. Interestingly, PIASy stabilized Msx1 protein, whereas deletion of the Msx1-interacting domain in PIASy abrogated the inhibition of tube formation and the stabilization of Msx1 protein. Our findings suggest the functional importance of PIASy-Msx1 interaction in Msx1-mediated angiogenesis inhibitio
Keyword
Msx1PIASyVEGFangiogenesisprotein stabilization
ISSN
2073-4409
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/cells9081854
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Files in This Item:

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.