A protective role of transmembrane channel-like proteins in human papillomavirus infection

Abstract

The identification of certain viral infections as the etiological agents responsible for inducing cancer has provided opportunities for prevention, detection, and treatments of these cancers. A rare genodermitosis known as Epidermodysplasia Verruciformis (EV) results in elevated levels of human papillomavirus (HPV) infection that frequently lead to squamous cell carcinoma (SCC) on sun-exposed areas of the skin. EV has long been thought to be a model for viral-induced cancer, but it was not until the year 2000 that mutations in two related genes were identified as being responsible for this disorder. Unfortunately, there is very little understanding of the function of their protein products: Transmembrane Channel-Like (TMC) proteins-6 and-8. We used Western blotting and immunohistochemical techniques to demonstrate that TMC8 is highly expressed in the skin and in particular the basal cells, which are key to HPV infection. We also demonstrate that TMC8 interacts with two proteins through the carboxyl terminus of TMC8: Non-Metastatic cell protein 1 (NME1) and Peroxiredoxin 2 (PRDX2). This study showed that TMC8 expression is affected by ROS generated by exposure to mitochondrial disruptors. We also tested the effect of TMC8 over expression on cell viability and found that it had a significant negative affect. Based on this data and the presentation of EV, the life cycle of HPV, and previous data, TMC8 appears to be a ROS-sensitive mediator of apoptosis. This study has produced valuable new data and also important new questions regarding TMC proteins. By continuing to expand this area of inquiry, hopefully knowledge can be gained to help relieve the suffering of those with EV, those with sporadic TMC mutations, and for immune compromised individuals that develop SCC that are associated with beta papillomaviruses.