THE NOVEL ATM-RELATED PROTEIN TRRAP IS AN ESSENTIAL COFACTOR FOR THE C-MYC AND E2F ONCOPROTEINS

The c-Myc and E2F transcription factors are among the most potent regu lators of cell cycle progression in higher eukaryotes. This report des cribes the isolation of a novel, highly conserved 434 kDa protein, des ignated TRRAP, which interacts specifically with the c-Myc N terminus and has homology to the ATM/PI3- kinase family. TRRAP also interacts s pecifically with the E2F-1 transactivation domain. Expression of trans dominant mutants of the TRRAP protein or antisense RNA blocks c-Myc- a nd E1A-mediated oncogenic transformation. These data suggest that TRRA P is an essential cofactor for both the c-Myc and E1A/E2F oncogenic tr anscription factor pathways.