@article{66796a988e3044dba7d02db086952ea6,
title = "HPV16 E6 augments Wnt signaling in an E6AP-dependent manner",
abstract = "In this study we investigated the effect of HPV16 E6 on the Wnt/β-catenin oncogenic signaling pathway. Luciferase reporter assays indicated that ectopically expressed E6 significantly augmented the Wnt/β-catenin/TCF-dependent signaling response in a dose-dependent manner. This activity was independent of the ability of E6 to target p53 for degradation or bind to the PDZ-containing E6 targets. Epistasis experiments suggested that the stimulatory effect is independent of GSK3β or APC. Coexpression, half-life determination, cell fractionation and immunofluorescence analyses indicated that E6 did not alter the expression levels, stability or cellular distribution of β-catenin. Further experiments using E6 mutants defective for E6AP binding and E6AP knockdown cells indicated the absolute requirement of the ubiquitin ligase E6AP for enhancement of the Wnt signal by E6. Thus, this study suggests a role for the E6/E6AP complex in augmentation of the Wnt signaling pathway which may contribute to HPV induced carcinogenesis.",
keywords = "E6, E6AP, GSK3β, HPV, TCF, Wnt signaling, β-Catenin",
author = "Hava Lichtig and Gilboa, {Daniella Avital} and Anna Jackman and Pinhas Gonen and Yaara Levav-Cohen and Ygal Haupt and Levana Sherman",
note = "Funding Information: We thank Drs. Arnona Gazit and Abraham Yaniv (Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University) for the Wnt3a, HFz1, β-catenin and dNTCF expression plasmids, Dr. Randall T. Moon (Howard Hughes Medical Institute, Department of Pharmacology and the Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine) for the superTOPFLASH/FOPFLASH plasmids, Dr. Chris Albanese (Departments of Oncology and Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center) for the cyclin D1 luciferase reporter, Dr. Elliot J. Androphy (Department of Medicine, University of Massachusetts Medical School) for the HPV16 E6 mutant G130V, L110Q, F2V expression plasmids, Dr. Massimo Tommasino (International Agency for Research on Cancer, WHO) for the HPV11, HPV18 and HPV16 E6 plasmids and Dr. Martin Scheffner (Department of Biology, University of Konstanz) for the E6AP encoding plasmid. Dr. Rina Rosin-Arbesfeld provided valuable comments on the manuscript. This work was funded by grants from the Leo Minz Fund for Cancer Research, Tel-Aviv University and the Cooperation Program in Cancer Research of the Deutsches Krebsforschungszentrum (DKFZ) and Israel's Ministry of Sciences and Technology (MOST) , Project No. 1841 awarded to L.S. H.L.K. performed this work in partial fulfillment of the requirements for the Ph.D. degree from the Sackler School of Medicine, Tel-Aviv University.",
year = "2010",
month = jan,
day = "5",
doi = "10.1016/j.virol.2009.10.011",
language = "אנגלית",
volume = "396",
pages = "47--58",
journal = "Virology",
issn = "0042-6822",
publisher = "Academic Press Inc.",
number = "1",
}
