Interaction with GATA transcription factors provides a mechanism for cell-specific effects of c-Fos.
c-Fos is a multifunctional transcription factor that is involved in cellular proliferation, differentiation and apoptosis. c-Fos is rapidly induced by a variety of hormones, growth factors and other extracellular stimuli, resulting in cell-specific responses. One potential mechanism underlying the cell-specific effects of c-Fos may be its ability to regulate gene expression through interaction with tissue-restricted transcription factors. We report here that c-Fos interacts with the cell-specific GATA proteins to potentiate their ability to transactivate target promoters, via GATA-binding sites. c-Fos is recruited to GATA proteins through direct interaction with their N-terminal activation domain. Neither the leucine zipper nor the DNA-binding domain of c-Fos is required for physical interaction with GATA proteins. Instead, a C-terminal domain located between amino acids 235 and 296, which is conserved in FosB but not in the nontransforming Fos family members, FosB/SF or Fra-1, is essential for c-Fos-GATA interaction. These data suggest that c-Fos may act as an inducible cofactor for cell-specific transcription factors and unravel a novel mechanism for transcriptional regulation by c-Fos, independent of the well-studied AP-1 pathway. The results also raise the possibility that dysregulated interaction with cell-specific transcription factors may be an important component in cellular transformation by nuclear oncogenes.
McBride
Kevin
K
Laboratoire de Développement et différenciation cardiaques, Institut de recherches cliniques de Montréal, 110, avenue des Pins Ouest, Montréal, QC, Canada H2W 1R7.
Charron
Frédéric
F
Lefebvre
Chantal
C
Nemer
Mona
M
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050991:GATA4 Transcription Factor; D011233:Precipitin Tests; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors