Repression of transforming growth factor β1 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 β1 (TGF-β1) 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-β1 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-β1 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-β1 promoter.
  • Author List

  • Datta PK; Bagchi S
  • Start Page

  • 25392
  • End Page

  • 25399
  • Volume

  • 269
  • Issue

  • 41