LACK OF TRANSCRIPTIONAL REPRESSION BY MAX HOMODIMERS

Max, a basic-helix-loop-helix-leucine zipper (bHLH-ZIP) protein, plays a central role in the transcriptional regulation of myc oncoprotein-r esponsive genes, Myc-max heterodimers bind to consensus E-box motifs n ear or within the promoters of these genes and activate gene expressio n, whereas heterodimers between max and members of the mad family of b HLH-ZIP proteins promote transcriptional repression. In contrast to al l other members of the myc network, max readily homodimerizes and bind s to identical E-box sites in vitro. However, the role for max homodim ers in transcriptional repression in vivo is unclear. Upstream stimula tory factor (USF) is a bHLH-ZIP protein which does not interact with m embers of the myc-max-mad family. By replacing the HLH-ZIP domain of m ax with that from USF, we created a chimeric protein, max(USF), which was indistinguishable from max with respect to its ability to homodime rize and bind DNA. As expected, however, max(USF) was unable to hetero dimerize with any of the tested max partner proteins and was incapable of suppressing c-myc target genes. Thus, transcriptional repression i s an exclusive property of max-mad heterodimers and cannot be achieved by max homodimers alone.