Fos C-terminal mutations block down-regulation of c-fos transcription following serum stimulation.
Transient accumulation of c-fos RNA following serum stimulation requires both a conserved 5' regulatory element and sequences at the 3' end of the gene. Here we show that mutations at the C terminus of Fos protein, of the type found in a virally-transduced actively transforming Fos variant, prevent the rapid down-regulation of c-fos transcription that occurs following serum-induced activation. Fos mutants that prevent down-regulation are dominant, acting in trans to prevent down-regulation of a co-transfected c-fos gene. Co-transfection experiments suggest that this effect is mediated by multiple sequence elements in the 5'-flanking region. Analysis of different Fos mutants showed that replacement of Fos sequences C-terminal to amino acid 337 with heterologous polypeptide, rather than simple truncation of the protein, is required to produce mutants defective in down-regulation. The results are discussed with reference to transformation by Fos.
Wilson
T
T
MRC Laboratory of Molecular Biology, MRC Centre, Cambridge, UK.
Treisman
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D002872:Chromosome Deletion; D003470:Culture Media; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D005809:Genes, Regulator; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D011519:Proto-Oncogenes; D014158:Transcription, Genetic; D014170:Transformation, Genetic
D003470:Culture Media; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos