THE EVES MOTIF MEDIATES BOTH INTERMOLECULAR AND INTRAMOLECULAR REGULATION OF C-MYB

The c-Myb transcription factor is a proto-oncoprotein whose latent tra nsforming activity can be unmasked by truncation of either terminus. B ecause both ends of Myb are involved in negative regulation, we tested whether they could associate in a two-hybrid assay and identified a c arboxy-terminal motif that interacts with the amino-terminal DNA-bindi ng domain. The ET;ES motif is highly conserved in vertebrate c-Myb pro teins and contains a known site of phosphorylation previously implicat ed in the negative regulation of c-Myb. Interestingly, a related EVES motif is present in p100, a ubiquitously expressed transcriptional coa ctivator found in diverse species, We show that p100 interacts with an d influences the activity of c-Myb, implicating it in the regulation o f c-Myb, differentiation, and cell growth. Our results suggest that My b is regulated by a novel mechanism in which intramolecular interactio ns and conformational changes control the intermolecular associations among Myb, p100, and the transcriptional apparatus.