Direct cloning of leucine zipper proteins: Jun binds cooperatively to the CRE with CRE-BP1.
The proto-oncogene products Fos and Jun form a stable heterodimeric complex that functions in transcriptional regulation by interacting with the DNA sequence known as the AP-1 site. Dimer formation occurs through the leucine zipper, a structural motif involving a heptad repeat of leucine residues that is conserved in several fos- and jun-related genes. We have employed a novel cloning strategy to isolate genes encoding proteins capable of forming complexes with Jun. The procedure involves direct screening of a lambda gt11 cDNA library with a biotinylated Jun polypeptide. One clone isolated in this manner encodes CRE-BP1, a leucine zipper-containing protein that binds to the cyclic AMP response element (CRE) as a homodimer. CRE-BP1 also forms heterodimers with Jun but not with Fos. Jun binds cooperatively to the CRE in association with CRE-BP1. Thus, the DNA-binding specificity and affinity of Jun are modulated by association with Fos or with CRE-BP1.
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Department of Molecular Oncology & Virology, Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
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Curran
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D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015723:Gene Library; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D015342:DNA Probes; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases