title: An RNA Aptamer Targets the PDZ-Binding Motif of the HPV16 E6 Oncoprotein.
abstract: Human papillomavirus 16 (HPV16) is a high-risk DNA tumour virus which is the primary causative agent of cervical cancer. Cell transformation arises from deregulated expression of the E6 and E7 oncogenes. E6 has been shown to bind a number of cellular proteins, including p53 and proteins containing a PDZ domain. This study reports the first RNA aptamers to E6. These have been employed as molecular tools to further investigate E6-p53 and E6-PDZ interactions. This study is focussed on two aptamers (termed F2 and F4) which induced apoptosis in cells derived from an HPV16-transformed cervical carcinoma. The molecules were able to inhibit the interaction between E6 and PDZ1 from Magi1, with F2 being the most effective inhibitor. Neither of the aptamers inhibited E6-p53 interaction or p53 degradation. This study shows the specificity of this approach and highlights the potential benefits of the E6 aptamers as potential therapeutic or diagnostic agents in the future.
authors: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. belyaeta@hotmail.com.
authors: Tamara A
authors: TA
authors: Belyaeva
authors: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. c.nicol@leeds.ac.uk.
authors: Clare
authors: C
authors: Nicol
authors: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. bs09oc@leeds.ac.uk.
authors: Ozlem
authors: O
authors: Cesur
authors: UMR 7242 CNRS-Université de Strasbourg, Ecole Supérieure de Biotechnologie, Boulevard Sébastien Brant, Illkirch 67412, France. gilles.trave@unistra.fr.
authors: Gilles
authors: G
authors: Travé
authors: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. g.e.blair@leeds.ac.uk.
authors: George Eric
authors: GE
authors: Blair
authors: School of Molecular and Cellular Biology, Faculty of Biological Sciences and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK. n.j.stonehouse@leeds.ac.uk.
authors: Nicola J
authors: NJ
authors: Stonehouse