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

Resistance to the growth inhibitory effects of transforming growth factor beta (TGF beta) has been associated with decreased levels of the TGF beta type II receptor (T beta R-II) and has been correlated with tumorigenicity. Previously, 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 promoter activity. In this study, we show that the CDP/Cut (CCAAT displacement protein) transcription factor, a transcriptional repressor, binds both the wild 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 constructs. Increased binding of the CDP/Cut repressor protein, as a result of a mutation at position -364, represents a novel mechanism of regulation in a neoplastic cell of the promoter of a turner suppressor gene, T beta R-II. (C) 1999 Academic Press.