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MafA has strong cell transforming ability but is a weak transactivator

Makoto Nishizawa1, Kohsuke Kataoka, Peter K Vogt

  • 1Department of Molecular and Experimental Medicine, BCC239, The Scripps Research Institute, La Jolla, CA, 92037, USA.

Oncogene
|September 13, 2003
PubMed

Insights

MafA and MafB proteins, part of the Maf family, were studied for their roles in cell transformation. MafA unexpectedly showed the strongest cell-transforming ability, linked to its DNA-binding domain.

Area of Science:

  • Molecular Biology
  • Oncology
  • Virology

Background:

  • The avian oncogenic retrovirus AS42 encodes the v-Maf oncoprotein, a nuclear bZip protein.
  • Cellular Maf proteins (c-Maf, MafA, MafB) are related bZip proteins involved in gene regulation.
  • The AP-1 transcription factor binding site is recognized by v-Maf.

Purpose of the Study:

  • To compare the transactivation and cell transformation capabilities of MafA, MafB, and c-Maf proteins.
  • To investigate the molecular mechanisms underlying Maf protein-induced cell transformation.
  • To develop regulatable systems for studying Maf-mediated cellular responses.

Main Methods:

  • Expression of MafA, MafB, and c-Maf proteins in chicken embryo fibroblasts.
  • Reporter gene assays to measure transactivation activity.
  • Construction of MafA-MafB chimeras and mutagenesis to identify functional domains.
  • Phosphorylation site analysis of Maf proteins.
  • Generation of MafA-estrogen receptor fusion proteins for hormone-dependent studies.

Main Results:

  • All tested Maf proteins induced cellular transformation in chicken embryo fibroblasts.
  • MafA exhibited significantly weaker transactivation activity compared to other Maf proteins.
  • MafA demonstrated the strongest cell transformation activity, correlated with its DNA-binding domain.
  • Phosphorylation of specific serine residues in MafA's transactivation domain influenced its activity.
  • MafA-estrogen receptor fusion proteins displayed tightly hormone-dependent cell transformation.

Conclusions:

  • The DNA-binding domain of MafA is critical for its potent cell-transforming ability.
  • Both DNA-binding and phosphorylation events regulate MafA's transactivation and transformation functions.
  • Regulatable MafA constructs enable detailed kinetic analysis of target gene responses and direct/indirect target discrimination.

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