Journal article

HPV16 E6 and E6AP differentially cooperate to stimulate or augment Wnt signaling

Sophia Sominsky, Yael Kuslansky, Beny Shapiro, Anna Jackman, Ygal Haupt, Rina Rosin-Arbesfeld, Levana Sherman



The present study investigated the roles of E6 and E6AP in the Wnt pathway. We showed that E6 levels are markedly reduced in cells in which Wnt signaling is activated. Coexpression of wild-type or mutant E6AP (C820A) in Wnt-activated cells stabilized E6 and enhanced Wnt/β-catenin/TCF transcription. Expression of E6AP alone in nonstimulated cells elevated β-catenin level, promoted its nuclear accumulation, and activated β-catenin/TCF transcription. A knockdown of E6AP lowered β-catenin levels. Coexpression with E6 intensified the activities of E6AP. Further experiments proved that E6AP/E6 stabilize β-catenin by protecting it from proteasomal degradation. This function was dependent on the cat..

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Awarded by Israel Science Foundation

Funding Acknowledgements

We are grateful to Dr. David Pim (International Centre for Genetic Engineering and Biotechnology, Trieste, Italy), Dr. L Gissmann (DKFZ, Germany) and Dr. M. Scheffner (Department of Biology, University of Konstanz, Germany) for kindly providing the expression plasmids for 16E7, E6opt and E6AP, respectively. This study was supported by Grant no. 1253-10 from the Israel Science Foundation, awarded to LS. This work was done in partial fulfillment of the requirements for M.Sc. degree of BS and Ph.D. degrees of SS and YK, Sackler Faculty of Medicine, Tel-Aviv University.