Myc and Max proteins possess distinct transcriptional activities

THE MyC family proteins are thought to be involved in transcription1,2 because they have both a carboxy-terminal basic-helix-loop-helix-zipper (bHLH-Z) domain, common to a large class of transcription factors, and an amino-terminal fragment which, for c-Myc, has transactivating function when assayed in chimaeric constructs4. In addition, c-, N- and L-Myc proteins heterodimerize, in vitro and in vivo, with the bHLH-Z protein Max5-8. In vitro, Max homodimerizes but preferentially associates with Myc, which homodimerizes poorly5,6. Furthermore Myc-Max heterodimers specifically bind the nucleotide sequence CACGTG9 with higher affinity than either homodimer alone5. The identification of Max and the specific DNA-binding activities of Myc and Max provides an opportunity for directly testing the transcriptional activities of these proteins in mammalian cells. We report here that Myc overexpression activates, whereas Max overexpression represses, transcription of a reporter gene. Max-induced repression is relieved by overexpression of c-Myc. Repression requires the DNA-binding domain of Max, whereas relief of repression requires the dimerization and transcriptional activation activities of Myc. Both effects require Myc-Max-binding sites in the reporter gene.