title: Human papillomavirus carcinogenesis: an identity crisis in the retinoblastoma tumor suppressor pathway.
abstract: Viruses are obligate intracellular parasites and need to reprogram host cells to establish long-term persistent infection and/or to produce viral progeny. Cellular changes initiated by the virus trigger cellular defense responses to cripple viral replication, and viruses have evolved countermeasures to neutralize them. Established models have suggested that human papillomaviruses target the retinoblastoma (RB1) and TP53 tumor suppressor networks to usurp cellular replication, which drives carcinogenesis. More recent studies, however, suggest that modulating the activity of the Polycomb family of transcriptional repressors and the resulting changes in epigenetic regulation are proximal steps in the rewiring of cellular signaling circuits. Consequently, RB1 inactivation evolved to tolerate the resulting cellular alterations. Therefore, epigenetic reprograming results in cellular "addictions" to pathways for survival. Inhibition of such a pathway could cause "synthetic lethality" in adapted cells while not markedly affecting normal cells and could prove to be an effective therapeutic approach.
authors: Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA karl.munger@tufts.edu.
authors: Karl
authors: K
authors: Munger
authors: Molecular, Cell, and Developmental Biology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California-Los Angeles, Los Angeles, California, USA.
authors: D Leanne
authors: DL
authors: Jones
mesh_terms: D016923:Cell Death; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D027383:Papillomaviridae / Q000276:immunology* / Q000502:physiology*; D063146:Polycomb-Group Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D063146:Polycomb-Group Proteins; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53