v-Myc, but not Max, possesses domains that function in both transcription activation and cellular transformation.
Deregulated expression of myc gene family members is associated with the development of malignant neoplasms in several species. Despite the evidence linking expression of this family of nuclear proteins with the proper control of cellular growth and development, the function of the myc protein remains unknown. Intrigued by the observed structural similarity between the myc protein and several eukaryotic transcription factors, we have investigated the ability of the MC29 viral myc protein to activate transcription of a heterologous promoter in C3H10T1/2 cells. Overlapping portions of v-myc coding sequences were inserted 3' to the yeast GAL4 DNA-binding domain and tested for their ability to activate transcription of a chloramphenicol acetyl transferase reporter gene containing GAL4 binding sites. Two transcription activation domains were identified within the amino terminus of v-Myc. The importance of these regions for cellular transformation was examined using ras/myc co-transformation assays. Our results demonstrate that deletion of either of the transcription activation domains, or the DNA-binding and protein oligomerization domains, abolishes the ability of v-Myc to cooperate with Ras to transform C3H10T1/2 cells. Similarly, we investigated whether Max, the protein-binding partner of Myc, also possesses the potential to activate transcription. Interestingly, chimeric GAL4/Max proteins were not functional in our assays, suggesting that the potential of the Myc-Max complex to influence gene expression and function in cellular transformation relies primarily on sequences found within the amino terminus of Myc.
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Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.
Taparowsky
E J
EJ
D050976:Basic-Leucine Zipper Transcription Factors; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D016274:Oncogene Protein p55(v-myc) / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000235:genetics*
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; C067850:Myc associated factor X; D016274:Oncogene Protein p55(v-myc); D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors