Association of Human Papillomavirus Types 16 and 18 E6 Proteins with p53

Abstract

Human papillomavirus type 16 (HPV-16) is a DNA tumor virus that is associated with human anogenital cancers and encodes two transforming proteins, E6 and E7. The E7 protein has been shown to bind to the retinoblastoma tumor suppressor gene product, pRB. This study shows that the E6 protein of HPV-16 is capable of binding to the cellular p53 protein. The ability of the E6 proteins from different human papillomaviruses to form complexes with p53 was assayed and found to correlate with the in vivo clinical behavior and the in vitro transforming activity of these different papillomaviruses. The wild-type p53 protein has tumor suppressor properties and has also been found in association with large T antigen and the E1B 55-kilodalton protein in cells transformed by SV40 and by adenovirus type 5, respectively, providing further evidence that the human papillomaviruses, the adenoviruses, and SV40 may effect similar cellular pathways in transformation.

RETRACTED ARTICLE: E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage

“…A number of cellular targets of the viral oncogenes of anogenital viruses have been identi®ed. These include the Rb and p53 proteins which are targeted by the viral E7 and E6 genes respectively (Dyson et al, 1989;Werness et al, 1990). The p53 tumour suppressor protein plays a pivotal role in cellular responses to stress factors such as DNA damage or hypoxia, principally through an induction of either cell cycle arrest or apoptosis (reviewed in Amundsen et al, 1998).…”

Hepatitis B virus-X protein upregulates the expression of p21wafl/cipl and prolongs G1→S transition via a p53-independent pathway in human hepatoma cells

“…A direct dose-dependent apoptotic function of HBV-X has been demonstrated in transiently transfected liver cell lines (Terradillos et al, 1998). HBV-X protein acutely sensitizes cells to apoptotic killing when expressed during viral replication independent of other genes (Werness et al, 1990;Su and Schneider, 1997;Slagle et al, 1996;Elmore et al, 1997). Cells that were resistant to apoptotic killing by high doses of tumor necrosis factor-a, a cytokine associated with liver damage during HBV infection, were made sensitive to very low doses of TNF-alpha by HBV-X (Su and Schneider, 1997).…”

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

“…6 [26,27]. This results in a compromised ability of the host cell to engage cell cycle checkpoints and apoptotic responses.…”