Beta Human Papillomavirus 8E6 Attenuates LATS Phosphorylation after Failed Cytokinesis
Dalton Dacus, Celeste Cotton, Tristan X. McCallister, Nicholas A. Wallace
Abstract
β-HPVs contribute to cSCC development in immunocompromised populations. However, it is unclear if these common cutaneous viruses are tumorigenic in the general population. Thus, a more thorough investigation of β-HPV biology is warranted. If β-HPV infections do promote cSCCs, they are hypothesized to destabilize the cellular genome. In vitro data support this idea by demonstrating the ability of the β-HPV E6 protein to disrupt DNA repair signaling events following UV exposure. We show that β-HPV E6 more broadly impairs cellular signaling, indicating that the viral protein dysregulates the HP. The HP protects genome fidelity by regulating cell growth and apoptosis in response to a myriad of deleterious stimuli, including failed cytokinesis. After failed cytokinesis, β-HPV 8E6 attenuates phosphorylation of the HP kinase (LATS). This decreases some, but not all, HP signaling events. Notably, β-HPV 8E6 does not limit senescence associated with failed cytokinesis.