MafA has strong cell transforming ability but is a weak transactivator.
The maf oncogene of the avian oncogenic retrovirus AS42 encodes a nuclear bZip protein, v-Maf, that recognizes sequences related to the AP-1 target site. The corresponding cellular protein, c-Maf belongs to a family of related bZip proteins together with MafA and MafB. In this paper, we compare the transactivation and cell transforming abilities of MafA and MafB along with two forms of the c-Maf protein. These proteins induce cellular transformation when expressed in chicken embryo fibroblasts. In reporter assays, MafA is a much less effective transactivator than the other Maf proteins, but unexpectedly shows the strongest activity in cell transformation. Chimeras of MafA and MafB correlate the strong cell transforming ability of MafA with its DNA-binding domain. The DNA-binding domain of MafA is also correlated with weak transactivation. Additional mutagenesis experiments show that transactivation and transformation by MafA are also controlled by phosphorylation of two conserved serine residues in the transactivation domain. Finally, we constructed MafA-estrogen receptor fusion molecules that show tightly hormone-dependent cell transforming ability. These regulatable constructs permit a kinetic characterization of target gene responses and facilitate discrimination between direct and indirect targets.
Nishizawa
Makoto
M
Department of Molecular and Experimental Medicine, BCC239, The Scripps Research Institute, La Jolla, CA, 92037, USA.
Kataoka
Kohsuke
K
Vogt
Peter K
PK
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D001665:Binding Sites; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D004958:Estradiol / Q000494:pharmacology; D051258:MafB Transcription Factor; D008969:Molecular Sequence Data; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D030161:Avian Proteins; D004268:DNA-Binding Proteins; D051258:MafB Transcription Factor; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C091157:maf-B protein, chicken; D013629:Tamoxifen; C016601:afimoxifene; D012694:Serine; D004958:Estradiol; D004247:DNA