Emerging roles of DNA tumor viruses in cell proliferation: new insights into genomic instability.
The small DNA virus proteins E1A and E1B from human Adenovirus, E6 and E7 from human papillomavirus, and large T and small T antigens from SV40, are multifaceted molecular tools that can carry out an impressive number of tasks in the host cell. These viral factors, collectively termed 'oncoproteins' for their ability to induce cancer, can be viewed as paradigmatic oncogenic factors which can disrupt checkpoint controls at multiple levels--they interfere with both 'gatekeeper' cellular functions, including major control pathways of cell cycle and apoptosis, and with 'caretaker' functions, thereby inducing mitotic abnormalities and increasing genomic instability. Both E1A and E7 have been recently found to interact physically with the Ran GTPase. This interaction is key in uncoupling the centrosome cycle from the cell cycle, highlighting a direct link between viral infection and the induction of genomic instability. Further expanding our current knowledge in this field will be crucial to elucidate viral strategies leading to cellular transformation and cancer progression, as well as design novel preventive or therapeutic approaches to human cancer.
Lavia
Patrizia
P
Institute of Molecular Biology and Pathology, CNR National Research Council, Rome, Italy.
Mileo
Anna Maria
AM
Giordano
Antonio
A
Paggi
Marco G
MG
D017500:Adenovirus E1A Proteins / Q000235:genetics; D002455:Cell Division; D018385:Centrosome / Q000648:ultrastructure; D004263:DNA Tumor Viruses / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000821:virology; D015513:Oncogene Proteins / Q000235:genetics; D014412:Tumor Virus Infections / Q000235:genetics* / Q000473:pathology*; D020931:ran GTP-Binding Protein / Q000235:genetics
D017500:Adenovirus E1A Proteins; D015513:Oncogene Proteins; D020931:ran GTP-Binding Protein