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A ubiquitous nuclear protein stimulates the DNA-binding activity of fos and jun indirectly

C Abate1, D Luk, T Curran

  • 1Department of Molecular Oncology and Virology, Roche Research Center, Nutley, New Jersey 07110.

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|October 1, 1990
PubMed

Insights

A nuclear protein significantly enhances the DNA-binding activity of fos-jun heterodimers and jun-jun homodimers. This protein indirectly regulates the DNA-binding function of these proto-oncogene transcription factors.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Protein-DNA Interactions

Background:

  • Proto-oncogenes c-fos and c-jun encode nuclear proteins (Fos and Jun) that form heterodimeric complexes.
  • These complexes regulate gene transcription by binding to activator protein-1 (AP-1) sites.
  • Previously, Fos and Jun proteins expressed in E. coli showed efficient dimerization but low DNA-binding activity.

Purpose of the Study:

  • To investigate the factors influencing the DNA-binding activity of Fos-Jun heterodimers and Jun-Jun homodimers.
  • To identify potential regulators of proto-oncogene transcription factor activity.

Main Methods:

  • Expression and purification of Fos and Jun polypeptides.
  • Analysis of protein dimerization using biochemical assays.
  • Electrophoretic mobility shift assays (EMSAs) to assess DNA-binding activity.
  • Investigation of the role of a ubiquitous nuclear protein in modulating DNA binding.

Main Results:

  • Fos-Jun heterodimers and Jun-Jun homodimers exhibit low DNA-binding activity when expressed in E. coli.
  • A ubiquitous nuclear protein dramatically stimulates the DNA-binding activity of these dimers.
  • The stimulating nuclear protein does not appear to be part of the DNA-protein complex and does not alter DNA-binding specificity.

Conclusions:

  • A ubiquitous nuclear protein plays a crucial role in regulating the DNA-binding activity of Fos and Jun proteins.
  • This regulation appears to be indirect, suggesting a co-factor mechanism.
  • These findings provide insights into the complex regulation of gene transcription by proto-oncogene products.

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