Smith-McCune K, Kalman D, Robbins C, Shivakumar S, Yuschenkoff L, Bishop JMIntranuclear localization of human papillomavirus 16 E7 during transformation and preferential binding of E7 to the Rb family member p130. Proc Natl Acad Sci USA 96: 6999-7004

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco CA 94115, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 07/1999; 96(12):6999-7004. DOI: 10.1073/pnas.96.12.6999
Source: PubMed


To study intracellular pathways by which the human papillomavirus 16 oncogene E7 participates in carcinogenesis, we expressed an inducible chimera of E7 by fusion to the hormone-binding domain of the estrogen receptor. The chimeric protein (E7ER) transformed rodent fibroblast cell lines and induced DNA synthesis on addition of estradiol. In coimmunoprecipitation experiments, E7ER preferentially bound p130 when compared to p107 and pRb. After estradiol addition, E7ER localization changed to a more intense intranuclear staining. Induction of E7 function was not correlated with binding to p130 or pRb but rather with intranuclear localization and modest induction of binding to p107.

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    • "The intracellular localization of high-risk and low-risk HPV E7s and whether there are differences in location that might explain functional differences are not completely established. Using tagged HPV 16 E7 and immunofluorescence, the E7 protein was found mainly in the nucleus (Smith-McCune et al., 1999). By immunofluorescence, both untagged high-risk and low-risk HPV E7 proteins are mostly nuclear but only the low-risk HPV E7 co-localizes with PML in PML oncogenic domains (PODs) while the high-risk HPV E7 is distributed more diffusely (Guccione et al., 2002). "
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    ABSTRACT: The oncogenic potential of papillomaviruses (PVs) has been appreciated since the 1930s yet the mechanisms of virally-mediated cellular transformation are still being revealed. Reasons for this include: a) the oncoproteins are multifunctional, b) there is an ever-growing list of cellular interacting proteins, c) more than one cellular protein may bind to a given region of the oncoprotein, and d) there is only limited information on the proteins encoded by the corresponding non-oncogenic PVs. The perspective of this review will be to contrast the activities of the viral E6 and E7 proteins encoded by the oncogenic human PVs (termed high-risk HPVs) to those encoded by their non-oncogenic counterparts (termed low-risk HPVs) in an attempt to sort out viral life cycle-related functions from oncogenic functions. The review will emphasize lessons learned from the cell culture studies of the HPVs causing mucosal/genital tract cancers.
    Full-text · Article · Mar 2012 · Virology
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    • "This discrepancy of Western blotting detecting cytoplasmic E7 and immunocytochemistry detecting both nuclear and cytoplasmic E7 has also been noted by others. It has been suggested that E7 may leak to the cytoplasmic fraction during cellular fractionation [24], [25]; a suggestion that we find to be very consistent with our comparative analyses. Immunocytochemistry samples on the other hand, were fixed in paraformaldehyde before analysis; preventing any leakage of E7 and permitting the detection of E7 in situ. "
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    ABSTRACT: E7 is one of the best studied proteins of human papillomavirus type 16, largely because of its oncogenic potential linked to cervical cancer. Yet the sub-cellular location of E7 remains confounding, even though it has been shown to be able to shuttle between the nucleus and the cytoplasm. Here we show with immunocytochemistry that E7 proteins are located in the nucleus and cytoplasm in sub-confluent cells, but becomes cytoplasmic in confluent cells. The change in E7's location is independent of time in culture, cell division, cell cycle phase or cellular differentiation. Levels of E7 are also increased in confluent cells as determined by Western blotting. Our investigations have also uncovered how different analytical techniques influence the observation of where E7 is localised, highlighting the importance of technical choice in such analysis. Understanding the localisation of E7 will help us to better comprehend the function of E7 on its target proteins.
    Full-text · Article · Jun 2011 · PLoS ONE
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    • "One causative agent in cervix carcinogenesis is infection with high risk human papilloma viral subtypes, including HPV-16 and -18 [20]. Expression of the oncoprotein, E6 and E7, have an established role in the initiation and growth of cervix cancer mediated by the inhibition of the products of the tumor suppressor genes p53 and pRB [21]. Human HPV genotype has some prognostic value in early-stage cervical cancers [22]; conversely positive HPV status correlates with reduced tumour aggressiveness and improved patient outcome, especially in Head & Neck tumors [23]. "
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