E6 proteins of α and β cutaneous HPV types differ in their ability to potentiate Wnt signaling

We recently showed that E6 protein of human papillomavirus (HPV) 16, a mucosal high-risk α-PV type, can potentiate Wnt/β-catenin/TCF signaling. Here we investigated the transcriptional activities of E6 proteins of cutaneous HPV types from the β and α genera. Results from reporter-gene assays showed that similar to HPV16 E6, E6 of HPV10, a cutaneous α-HPV type that is prevalent in skin warts, efficiently enhances and stimulates Wnt/β-catenin/TCF transcription. HPV10 E6 also effectively elevated the expression levels of β-catenin and promoted its nuclear accumulation. E6 proteins of β-HPV types 8, 24, 38 and 49, which are prevalent in skin cancer, exhibited lower activities in all tested functions. The differences in activity correlated with E6's competence to interact with the ubiquitin ligase E6AP. This study reveals a role for E6 proteins of diverse cutaneous HPV types in potentiation of Wnt/β-catenin signaling, irrespective of their carcinogenic potential. - Highlights: • β- and α-HPV E6 proteins were compared for their effect on β-catenin signaling. • Promotion of β-catenin transcription, stability and nuclear accumulation was tested. • E6 of HPV10, a wart associated α-HPV, showed the highest activity in all tested functions. • E6s of the cancer associated, β-HPVs (8, 24, 38, 49), exhibited lower activities. • The difference correlated with E6 ability to bind the ubiquitin ligase E6AP.