TATA-BINDING PROTEIN AND THE RETINOBLASTOMA GENE-PRODUCT BIND TO OVERLAPPING EPITOPES ON C-MYC AND ADENOVIRUS E1A PROTEIN

Using a protein binding assay, we show that the amino-terminal 204 ami no adds of the c-Myc protein interact directly with a key component of the basal transcription factor TFIID, the TATA box-binding protein (T BP). Essentially the same region of the c-Myc protein also binds the p roduct of the retinoblastoma gene, the RB protein. c-Myc protein coimm unoprecipitates with TBP in lysates of mammalian cells, demonstrating that the proteins are also complexed in vivo. A short peptide that spa ns the RB binding site of the E7 protein of human papilloma virus type 16 interferes with the binding of c-Myc to TBP. The same peptide also blocks binding of adenovirus E1A protein to TBP, suggesting that c-My c and E1A bind to RB and TBP through overlapping epitopes. Furthermore , we show that binding of RB to E1A prevents association of E1A with T BP. Our data suggest that one of the functions of RB and RB-like prote ins is to prevent interaction of viral and cellular oncoproteins, such as c-Myc and E1A, with TBP.