HPV types which belong to the beta-PV genus have been implicated in the development of non-melanoma skin cancer (NMSC). Our recent studies found that the E6 protein of HPV16, a mucosal high risk HPV type from the alpha genus, is capable to cooperate with the ubiquitin ligase E6AP to enhance or stimulate Wnt/beta-catenin/TCF transcription. In the present study we investigated the transcriptional activities of E6 proteins of diverse HPV types that infect the skin, both from the beta and alpha HPV genus.
Luciferase reporter gene assays, Western blots, immunoprecipitation and immunofluoresence analyses
Using reporter gene assays, we show that similar to 16E6, E6 of HPV10, an alpha HPV type which is prevalent in skin warts, is capable to efficiently augment as well as stimulate Wnt/beta-catenin/TCF transcription. Western blot and immunofluorescence analyses indicated that 10E6 also elevated efficiently the expression levels of beta-catenin and promoted its nuclear accumulation. E6 proteins of the beta HPV genus including HPV 8, 24, 38 and 49, exhibited lower activities in enhancement or stimulation of beta-catenin/TCF transcription, as well as reduced ability to stabilize β-catenin. The difference in levels of activity between the alpha and beta HPV E6 proteins correlated with the ability of the proteins to interact with E6AP.
This study revealed a role for E6 proteins of diverse skin associated HPV types in potentiating Wnt/beta-catenin/TCF signaling irrespective with their carcinogenic potential.