Adenoviral E1A Function through Myc

Abstract

The study of DNA tumor viruses has been invaluable in uncovering the cellular nodes and pathways that contribute to oncogenesis. Perhaps one of the best-studied oncoproteins encoded by a DNA tumor virus is adenovirus E1A, which modifies the function of key regulatory proteins such as retinoblastoma (Rb) and the chromatin remodeling protein p400. Although the interaction of E1A with Rb has long been known to target regulation of the E2F transcription factors, the downstream target of the E1A-p400 interaction has remained elusive. We have recently reported that a critical downstream link of the E1A-p400 nexus is the oncoprotein transcription factor c-Myc. Through its interaction with p400, E1A stabilizes Myc and promotes formation of Myc-p400 complexes on chromatin, leading to activation of Myc target genes. These findings point to an important role for p400 in Myc function and reveal that E1A drives oncogenesis by tapping into two important transcriptional networks: those of E2F and Myc.