title: Fos-Jun interaction: mutational analysis of the leucine zipper domain of both proteins.
abstract: Jun and Fos oncoproteins form a complex that regulates transcription from promoters containing AP-1 binding sites. The 'leucine zipper' domain of both Fos and Jun is necessary for the formation of the heterodimer, but the role of specific leucine residues is unclear. We have used site-specific mutagenesis to examine the contribution of individual leucine residues to the formation of a stable Fos-Jun protein complex and the binding of this complex to the AP-1 site. Mutation of a single leucine in either Fos or Jun had no effect on protein complex formation. Furthermore, mutations of two consecutive leucines in Jun did not interfere with heterodimer formation; however, in the case of Fos, two consecutive mutations resulted in an inability to form a heterodimer. Although mutagenesis of the first leucine of the heptad repeat had no effect on protein complex formation, this mutation in either Fos or Jun drastically reduced the affinity of the complex for DNA. Thus, both Fos and Jun contribute directly to the DNA-binding potential of the heterodimer.
authors.affiliation: Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92138.
authors.forename: L J
authors.initials: LJ
authors.lastname: Ransone
authors.forename: J
authors.initials: J
authors.lastname: Visvader
authors.forename: P
authors.initials: P
authors.lastname: Sassone-Corsi
authors.forename: I M
authors.initials: IM
authors.lastname: Verma
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D007930:Leucine / Q000502:physiology; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors / Q000235:genetics*
chemical_list: 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; D007930:Leucine