摘要
Smad2 and Smad3, the intracellular mediators of transforming growth factor β （TGF-β） signaling, are directly phosphorylated by the activated type I receptor kinase, and then shuttle from the cytoplasm into the nucleus to regulate target gene expression. Here, we report that the 70-kDa heat-shock protein （HSP70） interacts with Smad2 and decreases TGF-β signal transduction. Ectopic expression of HSPT0 prevents receptor-dependent phosphorylation and nuclear translocation of Smad2, and blocks TGF-β-induced epithelial-mesenchymal transition （EMT） in HaCat cells. Our findings reveal an essential role of HSP70 in TGF-β-induced epithelial-mesenchymal transition （EMT） by impeding Smad2 phosphorylation.
Smad2 and Smad3, the intracellular mediators of transforming growth factor β （TGF-β） signaling, are directly phosphorylated by the activated type I receptor kinase, and then shuttle from the cytoplasm into the nucleus to regulate target gene expression. Here, we report that the 70-kDa heat-shock protein （HSP70） interacts with Smad2 and decreases TGF-β signal transduction. Ectopic expression of HSPT0 prevents receptor-dependent phosphorylation and nuclear translocation of Smad2, and blocks TGF-β-induced epithelial-mesenchymal transition （EMT） in HaCat cells. Our findings reveal an essential role of HSP70 in TGF-β-induced epithelial-mesenchymal transition （EMT） by impeding Smad2 phosphorylation.
基金
supported by grants from the National Natural Science Foundation of China(No.90919058)
the National Basic Research Program of China(Nos. 2011 CB943904 and 2011 CB943800)
