Human cut-like repressor protein binds TGF beta type II receptor gene promoter

Resistance to the growth inhibitory effects of transforming growth factor b eta (TGF beta) has been associated with decreased levels of the TGF beta ty pe II receptor (T beta R-II) and has been correlated with tumorigenicity. P reviously, we reported an A --> G mutation at position -364 in the T beta R -II promoter in A431 tumor cells which results in reduced T beta R-II promo ter activity. In this study, we show that the CDP/Cut (CCAAT displacement p rotein) transcription factor, a transcriptional repressor, binds both the w ild type and the mutant TPR-II promoter. We also demonstrate that the A --> G mutation increases CDP/Cut binding affinity, and that overexpression of CDP/Cut reduces transcription from. T beta R-II promoter reporter construct s. Increased binding of the CDP/Cut repressor protein, as a result of a mut ation at position -364, represents a novel mechanism of regulation in a neo plastic cell of the promoter of a turner suppressor gene, T beta R-II. (C) 1999 Academic Press.