Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1.
Nuclear oncogene products have the potential to induce alterations in gene regulation leading to the genesis of cancer. The biochemical mechanisms by which nuclear oncoproteins act remain unknown. Recently, an oncogene, v-jun, was found to share homology with the DNA binding domain of a yeast transcription factor, GCN4. Furthermore, GCN4 and the phorbol ester-inducible enhancer binding protein, AP-1, recognize very similar DNA sequences. The human proto-oncogene c-jun has now been isolated, and the deduced amino acid sequence indicates more than 80 percent identity with v-jun. Expression of cloned c-jun in bacteria produced a protein with sequence-specific DNA binding properties identical to AP-1. Antibodies raised against two distinct peptides derived from v-jun reacted specifically with human AP-1. In addition, partial amino acid sequence of purified AP-1 revealed tryptic peptides in common with the c-jun protein. The structural and functional similarities between the c-jun product and the enhancer binding protein suggest that AP-1 may be encoded by c-jun. These findings demonstrate that the proto-oncogene product of c-jun interacts directly with specific target DNA sequences to regulate gene expression, and therefore it may now be possible to identify genes under the control of c-jun that affect cell growth and neoplasia.
Bohmann
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Howard Hughes Medical Institute, Department of Biochemistry, University of California, Berkeley, CA 94720.
Bos
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TJ
Admon
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Nishimura
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Vogt
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Tjian
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D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D001358:Avian Sarcoma Viruses / Q000235:genetics; D001483:Base Sequence; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005656:Fungal Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D005814:Genes, Viral; D006801:Humans; D008969:Molecular Sequence Data; D016759:Oncogene Protein p65(gag-jun); D009857:Oncogenes; D011494:Protein Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun; D011519:Proto-Oncogenes; D011994:Recombinant Proteins / Q000235:genetics; D012191:Retroviridae Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014158:Transcription, Genetic
D000906:Antibodies; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C000715470:MAS1 protein, human; D016759:Oncogene Protein p65(gag-jun); D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D012191:Retroviridae Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D004247:DNA; D011494:Protein Kinases