Maf and Jun nuclear oncoproteins share downstream target genes for inducing cell transformation.
The Maf oncoprotein is a basic leucine zipper (bZip)-bearing transcriptional activator that recognizes the Maf recognition element (MARE) DNA sequence. In this study, we investigated the role of Maf's transactivation function in cell transformation. Replacement of the conserved amino terminus transactivator domain of Maf by a heterologous and stronger transactivator domain (the acidic transactivator domain of VP16) resulted in enhanced transformation of chicken embryo fibroblast cells. In contrast, the fusing of a transcriptional repressor domain (Sin3 interaction domain of Mxi1) with the whole Maf protein masked the transactivator function of Maf, which in turn inhibited its transforming activity. Furthermore, the leucine zipper domain of Maf, which defines its dimer-forming specificity, was exchangeable with that of GCN4 yeast protein in terms of its transactivating and cell transforming activities. Thus, heterodimer formation with other bZip factors is not required for Maf's ability to transform. These results together suggest that transactivation through MARE is necessary for Maf-induced transformation and that there exist downstream target gene(s) for transformation. Since the MARE sequence overlaps with the recognition element of another bZip oncoprotein Jun, we assessed whether Jun and Maf induce cell transformation through activating the same genes. We thus constructed a mutated version of Jun that has a GCN4 leucine zipper and lacks the transactivator domain. This mutant repressed the cell transformation not only by Jun but also by Maf. Thus, Maf and Jun share downstream target gene(s) that are involved in cell transformation.
Kataoka
K
K
Department of Virology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. kkataoka@bio.titech.ac.jp
Shioda
S
S
Yoshitomo-Nakagawa
K
K
Handa
H
H
Nishizawa
M
M
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002467:Cell Nucleus / Q000201:enzymology* / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D005347:Fibroblasts; D017353:Gene Deletion; D005799:Genes, Dominant; D006801:Humans; D016350:Leucine Zippers; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism*; D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D015533:Transcriptional Activation; D014764:Viral Proteins
D004268:DNA-Binding Proteins; D016759:Oncogene Protein p65(gag-jun); D051256:Oncogene Protein v-maf; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D004247:DNA; D008156:Luciferases