1887

Abstract

An important characteristic of the E6 proteins derived from oncogenic associated human papillomaviruses (HPVs) is their ability to target the cellular tumour suppressor protein, p53, for ubiquitin mediated degradation. Several studies have attempted to address the important characteristics of both E6 and p53 for this activity , but the equivalent determinants have not been extensively assessed Indeed, recent studies indicate differences between the and the degradation assays. We have performed an extensive analysis of the ability of a range of HPV-18 E6 mutants to direct p53 degradation In addition, we have also compared the ability of HPV-18 E6 to direct the degradation of different oligomeric forms of p53 both in human and in murine cells. The results of these studies show that mutants of E6 exhibit very similar phenotypes both and In contrast, mutants of p53 show markedly different susceptibilities and to E6-induced degradation, and this is further affected by the nature of the cell type in which the assays are performed. Finally, using a cell line temperature sensitive for the E1 ubiquitin-activating enzyme we have been able to show directly that this enzyme is involved in the process of E6-mediated degradation of p53 .

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1998-08-01
2022-05-29
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