title: Human cut-like repressor protein binds TGFbeta type II receptor gene promoter.
abstract: 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.
authors.affiliation: 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.
authors.forename: R J
authors.initials: RJ
authors.lastname: Jackson
authors.forename: S J
authors.initials: SJ
authors.lastname: Antonia
authors.forename: K L
authors.initials: KL
authors.lastname: Wright
authors.forename: N S
authors.initials: NS
authors.lastname: Moon
authors.forename: A
authors.initials: A
authors.lastname: Nepveu
authors.forename: T
authors.initials: T
authors.lastname: Muñoz-Antonia
mesh_terms: 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
chemical_list: 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