Construction and expression of a monomeric c-Jun protein that binds and activates transcription of AP-1-responsive genes.
c-Jun is a typical member of the bZIP (basic zipper) family of dimeric transcriptional activators. These proteins contain a basic region responsible for DNA sequence recognition and a leucine zipper that mediates dimerization. bZIP proteins regulate a large number of important physiological functions and, therefore, present an interesting target for molecular interference and mimicry. As a step toward the development of peptide and nonpeptide analogs of such proteins, we constructed a derivative of c-Jun that binds DNA as a monomer. This construction was done by connecting a second basic region to the natural basic region of c-Jun by means of a short peptide loop. Although the polypeptide backbone of the second basic region has an inverted polarity relative to that of the natural basic region, the monomeric c-Jun protein binds DNA with reasonably high affinity and indistinguishable specificity from the wild-type, dimeric c-Jun protein. Furthermore, the monomeric c-Jun protein can activate transcription in vivo. These findings indicate that the polypeptide backbone of the basic region contributes little to sequence recognition and that the leucine zipper is not directly involved in transcriptional activation.
Deng
T
T
Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla 92093.
Karin
M
M
D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry*; D005786:Gene Expression Regulation; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors