Human cut-like repressor protein binds TGFbeta type II receptor gene promoter.
Resistance to the growth inhibitory effects of transforming growth factor beta (TGFbeta) has been associated with decreased levels of the TGFbeta type II receptor (TbetaR-II) and has been correlated with tumorigenicity. Previously, we reported an A --> G mutation at position -364 in the TbetaR-II promoter in A431 tumor cells which results in reduced TbetaR-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 TbetaR-II promoter. We also demonstrate that the A --> G mutation increases CDP/Cut binding affinity, and that overexpression of CDP/Cut reduces transcription from TbetaR-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 tumor suppressor gene, TbetaR-II.
Jackson
R J
RJ
Department of Biochemistry and Molecular Biology, Department of Internal Medicine, Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, Florida 33612, USA.
Antonia
S J
SJ
Wright
K L
KL
Moon
N S
NS
Nepveu
A
A
Muñoz-Antonia
T
T
D001665:Binding Sites; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins; D006801:Humans; D009369:Neoplasms / Q000209:etiology; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms
C080632:CUX1 protein, human; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D018125:Receptors, Transforming Growth Factor beta; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II