The Retinoblastoma Protein Region Required for Interaction with the E2F Transcription Factor Includes the T/E1A Binding and Carboxy-Terminal Sequences

摘要

ABSTRACTRecent experiments in understanding the mechanism of the retinoblastoma protein (RB) function have revealed the existence of several cellular proteins that are complexed with RB. One of these cellular proteins is the E2F transcription factor, which was originally identified due to its inducibility by E1A during an adenovirus infection. The E2F recognition sequence is found in the promoters of several cellular genes involved in growth control, including several oncogenes. In this report, we provide evidence that the interaction of E2F and RB is mediated through a region on RB where viral oncogenes such as SV40 T antigen and adenovirus E1A bind and where tumorigenic mutations also cluster. Additional carboxy-terminal sequences are also required for the interaction with E2F. These observations provide evidence for a direct connection between tumor suppressor function and the gene expression program leading to cellular growth regulation.