RB1 and neoplasm: Studying the interactions among human adenovirus E1A and SV40 large T antigen with Rb was essential for understanding the cellular tumor suppressor function [79] with the demonstration that a hypophosphorylated form of Rb negatively regulates G1 to S phase progression through the cell cycle by binding to and blocking the activity of E2F, a transcriptional factor activating several genes involved in cellular DNA replication.