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Virology. 2009 Feb 20;384(2):285-93. doi: 10.1016/j.virol.2008.09.034. Epub 2008 Dec 11.

The common mechanisms of transformation by the small DNA tumor viruses: The inactivation of tumor suppressor gene products: p53.

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1
Institute for Advanced Study, Princeton, NJ 08540, USA. alevine@ias.edu

Abstract

The small DNA tumor viruses, Polyoma virus, Simian Vacuolating Virus 40, the Papilloma viruses and the human Adenoviruses, were first described during a period of intense virus discovery (1930-1960s) and shown to produce tumors in animals. In each of these cases the viral DNA was shown to persist (commonly integrated into a host chromosome) and only a selected portion of this DNA was expressed as m-RNA and proteins in these cancers. The viral encoded tumor antigens were identified and shown to be required to both establish the tumor and maintain the transformed cell phenotype. The functions of these viral tumor antigens were explored and shown to have common features and mechanisms even though they appear to have evolved from diverse genes. The SV40 large tumor antigen, the human Papilloma virus E7 protein and the Adenovirus E1A protein were shown to bind to and inactivate the functions of the Retinoblastoma proteins in transformed cells. This resulted in the activation of the E2F and DP transcription factors and the entry of cells into the S-phase of DNA synthesis which was required for viral DNA replication. These events triggered the activation of p53 which promotes apoptosis of these virus infected cells limiting virus replication and tumor formation. These viruses responded by evolving and producing the SV40 large tumor antigen, the human Papilloma virus E6 protein and the Adenovirus E1b-55Kd protein which binds to and inactivates the p53 functions in both the infected cells and transformed cells. Some of the human Papilloma viruses and one of the Polyoma viruses have been shown to cause selected cancers in humans. Both the p53 tumor suppressor gene, which was uncovered in the studies with these viruses, and the retinoblastoma protein, have been shown to play a central role in the origins of human cancers via both somatic and germ line mutations in those genes.

PMID:
19081592
DOI:
10.1016/j.virol.2008.09.034
[Indexed for MEDLINE]
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