BS69, an adenovirus E1A-associated protein, inhibits the transcriptional activity of c-Myb

The carboxyl terminus of c-Myb contains a negative regulatory domain that i s absent in the v-Myb oncoprotein, but conserved among all the known Myb pr oteins of animals. This domain inhibits transcriptional activation by c-Myb in animal cells, but not in budding yeast, suggesting that additional prot ein(s) present in animal cells but not yeast are required for this negative regulatory function. A yeast two-hybrid screen identified BS69, an adenovi rus E1A-associated protein, as interacting with the carboxy-terminal region of c-Myb, BS69 contains regions of similarity to the PHD finger, the bromo domain, and the MYND domain, all of which are found in other proteins prese nt in high molecular weight complexes that regulate transcription and/or mo dify chromatin structure. Further study showed that BS69 inhibited the tran scriptional activity of c-Myb, that this inhibition was specific, that it m apped to the carboxyl termini of the two proteins and that it was dose-depe ndent. A direct interaction between these two proteins was observed in vitr o, Furthermore, the 289R E1A protein could inhibit the BS69-mediated decrea se in transcriptional activation by c-Myb, By analogy with the inhibition o f the Rb/E2F regulatory axis by EIA, we propose that a BS69/Myb regulatory circuit may also be a target of disruption during oncogenesis.