BS69, A NOVEL ADENOVIRUS E1A-ASSOCIATED PROTEIN THAT INHIBITS E1A TRANSACTIVATION

The adenovirus E1A gene products are nuclear phosphoproteins that can transactivate the other adenovirus early genes as well as several cell ular genes, and can transform primary rodent cells in culture. Transfo rmation and transactivation by E1A proteins is most likely to be media ted through binding to several cellular proteins, including the retino blastoma gene product pRb, the pRb-related p107 and p130, and the TATA box binding protein TBP. We report here the cloning of BS69, a novel protein that specifically interacts with adenovirus 5 E1A, BS69 has no significant homology to known proteins and requires the region that i s unique to the large (289R) E1A protein for high affinity binding. BS 69 and E1A proteins coimmunoprecipitate in adenovirus-transformed 293 cells, indicating that these proteins also interact in vivo. BS69 spec ifically inhibits transactivation by the 289R E1A protein, but not by the 243R E1A protein. BS69 also suppressed the E1A-stimulated transcri ption of the retinoic acid receptor in COS cells, but did not affect t he cellular E1A-like activity that is present in embryonic carcinoma c ells. Our data indicate that BS69 is a novel and specific suppressor o f E1A-activated transcription.