AN AMINO-TERMINAL DOMAIN OF MXI1 MEDIATES ANTI-MYC ONCOGENIC ACTIVITYAND INTERACTS WITH A HOMOLOG OF THE YEAST TRANSCRIPTIONAL REPRESSOR SIN3

Documented interactions among members of the Myc superfamily support a yin-yang model for the regulation of Myc-responsive genes in which tr ansactivation-competent Myc-Max heterodimers are opposed by repressive Mxi1-Max or Mad-Max complexes. Analysis of mouse mxi1 has led to the identification of two mxi1 transcript forms possessing open reading fr ames that differ in their capacity to encode a short aminoterminal alp ha-helical domain. The presence of this segment dramatically augments the suppressive potential of Mxi1 and allows for association with a ma mmalian protein that is structurally homologous to the yeast transcrip tional repressor SIN3, These findings provide a mechanistic basis for the antagonistic actions of Mxi1 on Myc activity that appears to be me diated in part through the recruitment of a putative transcriptional r epressor.