Repression of transforming growth factor beta 1 promoter by the adenovirus oncogene E1A. Identification of a unique GC-rich sequence as a target for E1A repression.

Academic Article

Abstract

  • The transforming growth factor beta 1 (TGF-beta 1) is a key regulator of proliferation and differentiation in a wide variety of cell types. It is a potent growth inhibitor for most epithelial, endothelial, lymphoid, and myeloid cells. In the present study, we showed that a DNA virus oncoprotein, E1A, strongly repressed the activity of the TGF-beta 1 promoter in a variety of cell lines. Interestingly, this repression was specific for 12 S E1A because 13 S E1A was much less active in this assay. Analysis of a series of E1A mutants showed that the repression was dependent on the amino terminus and the conserved region 1 of the E1A protein. To identify the target sequence for E1A repression in the TGF-beta 1 promoter, a series of mutant promoters were analyzed and a 10-base pair GC-rich sequence between -91 and -82 was found to be the major target for E1A repression of the promoter. Using chimeric reporter constructs, we provide evidence that the 10-base pair GC-rich sequence is sufficient to impart sequence-specific E1A repression to a heterologous promoter. Additionally, we suggest that the mechanism of E1A repression through this GC-rich element does not involve abrogation of the retinoblastoma control of the TGF-beta 1 promoter.
  • Published In

    Keywords

  • Adenovirus E1A Proteins, Adenovirus E2 Proteins, Animals, Base Sequence, Binding Sites, Cells, Cultured, Chloramphenicol O-Acetyltransferase, Conserved Sequence, DNA Mutational Analysis, Gene Expression, Gene Expression Regulation, Genes, Reporter, Humans, Mice, Mink, Molecular Sequence Data, Oncogenes, Promoter Regions, Genetic, Protein Binding, Recombinant Fusion Proteins, Species Specificity, Transcription, Genetic, Transforming Growth Factor beta
  • Author List

  • Datta PK; Bagchi S
  • Start Page

  • 25392
  • End Page

  • 25399
  • Volume

  • 269
  • Issue

  • 41