TGF-β Attenuates the Transactivation Activity of Ets-1 despite its Induction via the Inhibition of DNA Binding

抄録

We examined whether TGF-β affects the transactivation activity of Ets-1. TGF-β augmented ets-1 mRNA expression and Ets-1 protein synthesis in ECV304 cells to the level equivalent to bFGF. When the DNA binding activity of Ets-1 protein was examined, bFGF was found to enhance DNA-Ets complex formation, whereas TGF-β attenuated basal as well as bFGF-enhanced DNA-Ets complex formation. As a result, TGF-β attenuated the promoter activity driven by Ets-1. The DNA binding of Ets-1 protein was enhanced by the initial 4-hour bFGF treatment and the subsequent 8-hour cycloheximide treatment. When TGF-β replaced cycloheximide in the subsequent 8-hour treatment, TGF-β inhibited this bFGF-enhanced DNA-Ets complex formation. When TGF-β and cycloheximide were simultaneously added in the subsequent 8-hour treatment, the inhibitory effect of TGF-β on bFGF-enhanced DNA-Ets complex formation was completely abolished. These results suggest the possibility that TGF-β attenuates the transactivation activity of Ets-1 by inducing a protein that interferes with the binding of Ets-1 to the DNA binding site.