Human cytomegalovirus pp71: A new viral tool to probe the mechanisms of cell cycle progression and oncogenesis controlled by the retinoblastoma family of tumor suppressors

The DNA tumor virus oncogenes (adenovirus E1A, simian virus 40 (SV40) large T antigen, and papillomavirus E7) have been instrumental in illuminating the molecules and mechanisms of cell cycle progression and carcinogenesis. However, since these multifunctional proteins target so many important cellular regulators, it is sometimes difficult to establish the functional importance of any individual interaction. Perhaps a herpesvirus protein, newly defined as a cell cycle regulator, can help address these issues. Like the DNA tumor virus proteins, the human cytomegalovirus(HCMV)pp71 protein contains a retinoblastoma protein (Rb) binding motif (LxCxD), and stimulates DNA synthesis in quiescent cells. Unlike E1A, T antigen, and E7, pp71 expression does not induce apoptosis, nor does it cooperate to transform primary cells. Determining how pp71 induces cell cycle progression without invoking apoptosis or leading to cellular transformation may help in defining the signals that ultimately lead to these processes. (C) 2004 Wiley-Liss, Inc.