Structure-function analysis of the maf oncogene product, a member of the b-Zip protein family.
The v-maf oncogene, identified as the transforming gene of the avian retrovirus AS42, encodes a protein containing a b-Zip motif. From this structural feature, the v-Maf protein was expected to form a dimer and function as a nuclear DNA-binding protein. In this study, we demonstrate that this protein indeed localizes predominantly in the nucleus and forms a homodimer through its leucine zipper structure. To delineate the structural requirement for the transforming activity, we constructed and characterized a panel of v-maf mutants harboring various deletions or point mutations. A region of about 100 amino acid residues located near its carboxyl terminus, which contains the b-Zip motif, was found to be essential for the basal transforming activity of v-Maf on chicken embryo fibroblasts. On the other hand, the amino-terminal two-thirds of the v-Maf protein seems to play a role in potentiating the transforming activity of v-Maf. It was also found that the c-maf proto-oncogene, without any structural modification in its protein-coding region, could transform cells as efficiently as could the v-maf oncogene when transduced by a retroviral vector. Thus, it is probably deregulated expression that makes the v-maf gene oncogenic. In addition, we discovered one point mutation, altering the structure of the b-Zip domain, which further enhances the transforming activity of the v-maf oncogene. Such mutant will be useful in exploring the mechanism of action of the Maf protein.
Department of Viral Oncology, Cancer Institute, Tokyo, Japan.
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Kataoka
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Nishizawa
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Kawai
D000818:Animals; D001354:Avian Leukosis Virus / Q000235:genetics*; D001483:Base Sequence; D002451:Cell Compartmentation; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D066298:In Vitro Techniques; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes; D011485:Protein Binding; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics*; D014764:Viral Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D014764:Viral Proteins; C495606:v-Maf protein, Avian retrovirus AS42