Human papillomavirus type 16 E6/E7 upregulation of nucleophosmin is important for proliferation and inhibition of differentiation

Centre for Cancer Research and Cell Biology, Queen's University, Belfast BT9 7BL, United Kingdom.
Journal of Virology (Impact Factor: 4.65). 03/2010; 84(10):5131-9. DOI: 10.1128/JVI.01965-09
Source: PubMed

ABSTRACT The E6 and E7 oncoproteins of high-risk human papillomaviruses (HPVs) are together sufficient to cause cellular transformation. Nucleophosmin (NPM) was identified as a protein with increased levels in two-dimensional (2-D) gel analysis of human foreskin keratinocytes (HFKs) expressing E7 following methylcellulose-induced differentiation. Analysis of NPM expression in E7-expressing cells and E6- and E7-expressing cells in culture and in organotypic rafts confirmed the increased levels observed in 2-D gel analysis. The elevated expression of NPM was determined to be posttranscriptional and was attributed to increased v-akt murine thymoma viral oncogene (AKT) activity in the E6- and E7-expressing cells. Depletion of NPM caused a reduction in the replicative capacity of E7- and E6/E7-expressing HFKs and an increase in markers of differentiation. Also, the p53 and pRb tumor suppressor levels are increased with the knockdown of NPM in E6/E7-expressing cells, and, interestingly, p14(ARF) is relocalized from the nucleolus to the nucleoplasm and cytoplasm in these cells. The results show for the first time that NPM is required for the proliferation and inhibition of differentiation observed in HPV E6- and E7-expressing primary cells.

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Available from: Dennis J Mccance, Aug 03, 2015
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    • "shER was provided by D. Picard (Geneva University, Geneva, Switzerland) siRNA for IKK or IKK was purchased from Ambion, and the sequence used was previously published (Accardi et al., 2011). siRNA for HPV16E6E7 or E7 was purchased from Dharmacon and previously published (Tang et al., 2006; McCloskey et al., 2010). The ISRE Luciferase minimal promoter was purchased from Stratagene. "
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    • "The authors suggest that this might negatively affect the segregation of daughter cells into one basal and one suprabasal cell (Nguyen and Munger, 2009). Via AKT activation, high risk E7 upregulates nucleophosmin , a positive regulator of proliferation and negative regulator of differentiation (McCloskey et al., 2010). Although the authors previously showed that Rb was required for E7-induced AKT activity (Menges et al., 2006), knocking down Rb did not result in increased nucleophosmin. "
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