The disruption of cell cycle checkpoints by papillomavirus oncoproteins contributes to anogenital neoplasia.
Human cancer are characterized by the failure of cell cycle checkpoints resulting in genetic instability. Human papillomaviruses contribute to the development of anogenital malignancies because the E6 and R7 oncoproteins from high risk HPV types are able to disrupt the integrity of these checkpoints. HPV 16 E7 prevents suprabasal cells from exiting the cell cycle, thus increasing the pool of replicating cells that are available for additional 'hits'. Cells that suffer DNA of chromosome damage are not eliminated because E6 and E7 are able to bypass G1 and G2 damage-induced checkpoints. The activation, or inactivation, of additional cellular genes required for invasion and metastasis may not be a direct consequence of the E6/E7 oncoproteins.
Galloway
D A
DA
Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
McDougall
J K
JK
D000694:Anal Gland Neoplasms / Q000821:virology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D004249:DNA Damage; D005260:Female; D005833:Genital Neoplasms, Female / Q000821:virology*; D005834:Genital Neoplasms, Male / Q000821:virology*; D006801:Humans; D008297:Male; D009856:Oncogene Proteins, Viral / Q000502:physiology*; D027383:Papillomaviridae / Q000502:physiology*
D009856:Oncogene Proteins, Viral