Tohoku J. Exp. Med., 2001, 193 (4)

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

CHIKA IWASAKA-YAGI, MAYUMI ABE and YASUFUMI SATO

Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575

We examined whether TGF-b affects the transactivation activity of Ets-1. TGF-b 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-b attenuated basal as well as bFGF-enhanced DNA-Ets complex formation. As a result, TGF-b 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-b replaced cycloheximide in the subsequent 8-hour treatment, TGF-b inhibited this bFGF-enhanced DNA-Ets complex formation. When TGF-b and cycloheximide were simultaneously added in the subsequent 8-hour treatment, the inhibitory effect of TGF-b on bFGF-enhanced DNA-Ets complex formation was completely abolished. These results suggest the possibility that TGF-b attenuates the transactivation activity of Ets-1 by inducing a protein that interferes with the binding of Ets-1 to the DNA binding site.

Keywords —— ets-1; TGF-b; DNA binding; transactivation

© 2001 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2001, 193, 311-318

Address for reprints: Yasufumi Sato, Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryomachi, Aoba-ku, Sendai 980-8575, Japan.

e-mail: y-sato@idac.tohoku.ac.jp