Activation of the retinoblastoma gene expression by Bcl-3: implication for muscle cell differentiation

Oncogene. 1996 May 2;12(9):1837-45.

Abstract

The retinoblastoma (Rb) protein is a master regulator of cell cycle. Accumulating evidence suggests that elevation of Rb expression is a key event in differentiation of various cell types. However the mechanism of regulation of Rb expression is poorly understood. Here we report that the candidate oncoprotein Bcl-3, previously characterized as a member of the IkappaB family, activates transcription of the Rb gene, whose promoter has no typical kappaB sites. A target element for Bcl-3 that matches the consensus for the E4TF1/GABP transcription factor was identified. Bcl-3 was shown to promote tetramer formation of E4TF1. During muscle cell differentiation, increased bcl-3 expression was observed before the induction of the Rb mRNA. Transient expression of Bcl-3 in myoblasts was shown to induce expression of the endogenous Rb. Furthermore, expression of the antisense bcl-3 RNA in myoblasts suppressed induction of Rb and myogenic differentiation. These results suggest that Bcl-3 is an upstream regulator of Rb expression during differentiation of muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Cell Lymphoma 3 Protein
  • Base Sequence
  • Cell Differentiation / genetics
  • DNA
  • Gene Expression Regulation / physiology*
  • Genes, Retinoblastoma*
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Muscles / cytology*
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / physiology*
  • Transcription Factors
  • Tumor Cells, Cultured

Substances

  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • Proto-Oncogene Proteins
  • Transcription Factors
  • DNA