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The human retinoblastoma susceptibility gene promoter is positively autoregulated by its own product

Academic Article
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Overview

authors

  • Park, K.
  • Choe, J.
  • Osifchin, N. E.
  • Templeton, D. J.
  • Robbins, Paul D.
  • Kim, S. J.

publication date

  • 1994

journal

  • Journal of Biological Chemistry  Journal

abstract

  • The product of the retinoblastoma susceptibility gene is a 105-kDa protein that has properties of a cell cycle regulatory factor. Previous reports indicated that two distinct DNA-binding factors, RBF-1 and ATF, play an important part in the transcription of the human retinoblastoma gene (Rb). Recently, we demonstrated that pRb activates expression of the human transforming growth factor-beta 2 gene through ATF-2. Since the human Rb gene promoter also contains an ATF-2-like binding site, we examined whether pRb can regulate its own expression through ATF-2. Here we report that overexpression of Rb stimulates Rb promoter activity through the ATF binding site in a variety of different cell types. Mutation of the ATF binding site of the Rb promoter abolishes the Rb autoinduction. We have also determined that the carboxyl-terminal domain of pRb is responsible for the Rb autoinduction through ATF-2. Rb autoinduction may be important for maintaining the action of pRb during cell growth, and loss of autoinductibility may contribute to retinoblastoma.

subject areas

  • Activating Transcription Factors
  • Animals
  • Base Sequence
  • Binding Sites
  • Blood Proteins
  • Cell Line
  • DNA
  • Gene Expression Regulation
  • Genes, Retinoblastoma
  • Humans
  • Mink
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Promoter Regions, Genetic
  • Retinoblastoma Protein
  • Transcription Factors
  • Transcription, Genetic
  • Tumor Cells, Cultured
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

PubMed ID

  • 8119953
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Additional Document Info

start page

  • 6083

end page

  • 6088

volume

  • 269

issue

  • 8

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