INTERACTION OF C-MYC WITH THE PRB-RELATED PROTEIN P107 RESULTS IN INHIBITION OF C-MYC-MEDIATED TRANSACTIVATION

The product of the c-myc proto-oncogene, c-Myc, is a sequence-specific DNA binding protein with an N-terminal transactivation domain and a C -terminal DNA binding domain. Several lines of evidence indicate that c-Myc activity is essential for normal cell cycle progression. Since t he abundance of c-Myc during the cell cycle is constant, c-Myc's activ ity may be regulated at a post-translational level. We have shown prev iously that the N-terminus of c-Myc can form a specific complex with t he product of the retinoblastoma gene, pRb, in vitro. These data sugge sted a model in which pRb, or pRb-related proteins, regulate c-Myc act ivity through direct binding. We show here that the pRb-related protei n p107, but not pRb itself, forms a specific complex with the N-termin al transactivation domain of c-Myc in vivo. Binding of p107 to c-Myc c auses a significant inhibition of c-Myc transactivation. Expression of c-Myc releases cells from a p107-induced growth arrest, but not from pRb-induced growth arrest. Our data suggest that p107 can control c-My c activity through direct binding to the transactivation domain and th at c-Myc is a target for p107-mediated growth suppression.