THE CARBOXY-TERMINAL DOMAIN OF C-MYB ACTIVATES REPORTER GENE-EXPRESSION IN YEAST

We have shown previously that c-myb expressed in the yeast S. cerevisi ae mediated efficient transcriptional activation of reporter genes des igned with specific Myb Recognition Elements (MRE's), confirming that this proto-oncogene is able to function as a regulator of transcriptio n in that heterologous context. Here we show that in yeast, as in high er eucaryotic cells, the central domain of c-Myb displays transactivat ing capacity. In yeast, however, the carboxy-terminal region, defined as a negative regulatory domain in higher cells, activates transcripti on as well and appears to be a more potent transactivating domain than the central domain itself. Within this region two domains, namely C1 and C2, have been defined that contribute about equally to the activit y of the carboxy-terminal region. C1 spans the sequences missing in AM V v-myb while C2, which contains the leucine-zipper motif is specifica lly absent in the E26 v-myb in addition to C1. The c-Myb DNA-binding d omain itself has no effect on the level of transcription in yeast. We also show that AMV v-Myb stimulates gene expression in yeast with abou t half the efficiency of full length c-Myb. The fact that the carboxy- terminal region either stimulates or inhibits transactivation properti es of c-Myb, depending on the cellular context, stresses the participa tion of putative c-Myb partner proteins in Myb regulated processes and reopens the question of whether the oncogenic activation of c-myb is indeed due to the increased transactivation capacity of its onco deriv atives.