trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation.
Fos protein can trans-activate AP-1-dependent gene expression and trans-repress the c-fos promoter. Although we find that trans-repression is enhanced by coexpression of c-Jun, it does not require any of the AP-1 or ATF sites in the mouse c-fos promoter. A major target for repression is the serum response element (SRE). Fos mutants with an impaired leucine zipper are defective in trans-repression and transformation, suggesting that these functions involve the formation of Fos protein complexes. In contrast, mutations that abolish DNA binding of Fos enhance trans-repression but destroy the transforming potential of Fos. In addition, v-Fos protein efficiently transforms but is unable to trans-repress. These findings point to different mechanisms involved in trans-activation and trans-repression and suggest that trans-repression of the type described here is neither sufficient nor required for Fos-induced transformation.
Lucibello
F C
FC
Institut für Molekularbiologie und Tumorforschung, Philipps-Universität Marburg, Federal Republic of Germany.
Lowag
C
C
Neuberg
M
M
Müller
R
R
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D051379:Mice; D015345:Oligonucleotide Probes; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D015533:Transcriptional Activation; D014162:Transfection
D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011505:Protein-Tyrosine Kinases