Abstract 15537: E2F1 Suppresses Fibrosis Through Serine-threonine Kinase Receptor Associated Protein (Strap)
Background: E2F1 is best studied in cell-cycle control and cancer biology. Recently, we have disclosed a novel function of E2F1 that suppresses TGF-beta signaling pathway; however the underlying molecular mechanisms and physiological significance of this regulation remains unknown.
Methods and Results: In a proteomics approach, Flag-tagged Smad3 protein was overexpressed in the embryonic fibroblasts (MEF) isolated from wild-type (WT) and E2F1-null (E2F1-KO) mice, and the Smad3-interacting proteins were isolated by co-immunoprecipitation and identified by mass spectrometry. Notably, the serine-threonine kinase receptor-associated protein (Strap) was found associated with Smad3 in WT MEFs, but not in E2F1-KO MEFs. This is important because Strap has been shown as inhibitor of canonical TGF-beta signaling pathway by interacting with both TGF-beta receptor I and Smad7 to interfere with Smad2/3 activation. When analyzed by Western blotting, we found that the expression of Strap was significantly higher in WT MEFs than in E2F1-KO MEFs, and similar results were obtained in the cardiac and lung tissues of WT and E2F1-KO mice. Remarkably, both bleomycin and Ang II treatments resulted in a significantly greater degree of lung fibrosis in E2F1-KO mice than in WT mice.
Conclusion: Our results suggest that E2F1 suppresses tissue fibrosis through Strap expression and Strap-mediated repression of canonical TGF-beta signaling pathway.
Author Disclosures: D. Biyashev: None. C. Boriboun: None. J. Zhou: None. G. Qin: None.
This research has received full or partial funding support from the American Heart Association
- © 2014 by American Heart Association, Inc.