Proto-oncogene FosB: the amino terminus encodes a regulatory function required for transformation.
Overexpression of some members of the Fos gene family, including FosB, leads to transformation of established rodent fibroblasts. We have previously shown that transformation by FosB requires the presence of a C-terminal transcriptional activation domain. We now report that transformation by FosB also requires an intact DNA-binding domain composed of the functionally bipartite basic region and leucine zipper as well as sequences present in the N terminus that serve a regulatory function. Deletion of the N-terminal sequences results in proteins impaired in transcriptional activation and transformation. This region does not itself function as a transcriptional activation domain but instead regulates the transactivation functions present in the FosB-Jun complex. The requirement for this N-terminal region can be abolished by the presence of a strong constitutive activation domain. The primary sequence of the region that we have defined is highly conserved in the Fos family of proteins, suggesting functional conservation.
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Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186-5800.
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D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016762:Genes, fos; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009363:Neoplasm Proteins / Q000032:analysis; D009838:Oligodeoxyribonucleotides; D010957:Plasmids; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D015500:Chloramphenicol O-Acetyltransferase; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3