Transcriptional activities of the Myc and Max proteins in mammalian cells.
The myc family of oncogenes exhibit deregulated expression in a host of neoplasias. Though the molecular function of the Myc protein in both normal and tumorigenic cells has remained uncertain, it has been postulated to play a role in gene transcription on the basis of amino acid homologies with known transcription factors such as MyoD (Lüscher & Eisenman, 1990). We report here the direct testing of full-length Myc and its dimerization partner, Max, on the transcriptional activity of reporter genes bearing Myc/Max binding sites. Such reporter constructs display an endogenous level of activity in transient transfections which is dependent on the presence of the CACGTG sequence. Exogenous expression of myc results in modest activation of reporter gene transcription. Similar overexpression of max results in a repression of reporter gene activity, an effect which is reversed by co-expression with c-myc. Max repression is dependent on an intact DNA binding region, while Myc activation depends on both the N-terminal activation and the C-terminal dimerization domains. These results suggest a model in which Max homodimers can act as as repressors, and Myc-Max heterodimers as activators, of potential target genes.
Kretzner
L
L
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blackwood
E M
EM
Eisenman
R N
RN
D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010957:Plasmids; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014157:Transcription Factors; D014158:Transcription, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499330:MAX protein, human; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D004247:DNA