Mutagenesis of the DNA contact site in Fos protein: compatibility with the scissors grip model and requirement for transformation.
To elucidate the mechanisms involved in the transformation by fos we have initiated a study pertaining to the identification of molecular functions of Fos protein that are crucial for transformation. We have previously reported that the presence of an intact leucine zipper in Fos is an absolute requirement for the induction of transformation, but that the autorepression function of Fos is dispensable. We now show that Fos protein also needs an intact DNA (TRE)-binding site to be able to transform. Amino acid substitutions in this domain of Fos which impair DNA binding also destroy the transforming potential of Fos, suggesting that the interaction of Fos-Jun complexes with TREs may be a crucial part of Fos-induced transformation. This hypothesis is further strengthened by our observation that Fos and Jun can cooperate in the induction of transformation. We show that a Fos protein which contains a Jun leucine zipper and is thus capable of dimerization is still dependent on the presence of exogenous Jun to induce transformation. The critical positions in the Fos DNA-binding site include those which the 'scissors grip' model predicts to be crucial, although the DNA-binding site in Fos seems to extend beyond the basic region into an adjacent cluster of acidic amino acids.
Neuberg
M
M
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Germany.
Schuermann
M
M
Müller
R
R
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D016350:Leucine Zippers / Q000235:genetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors / Q000235:genetics; D014170:Transformation, Genetic
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D004247:DNA