Cutaneous Human Papillomaviruses as Co-Factors in Non-Melanoma Skin Cancer
Abstract
We have made substantial strides in our efforts to better define Beta-HPV E6s ability to augment the mutagenic potential of genome destabilizing events. We show that Beta-HPV E6 changes signaling events in 3 pathways (Nucleotide Excision Repair or NER, Hippo Pathway or HP and Non-Homologous End Joining or NHEJ) that protect genome fidelity. It attenuates NER signaling by decreasing XPA phosphorylation, accumulation and nuclear translocation. It decreases LATS2 phosphorylation in the HP, resulting in aberrant responses to failed cytokinesis. Beta-HPV E6 also makes cells more reliant on DNApk and the NHEJ pathway. These findings are largely dependent on the viral oncogenes ability to bind and destabilize p300. We also found p300 independent inhibition of the cellular DNA repair response. Specifically, we show p300-independent sensitivity to Zeocin, a radiation mimetic. We also have preliminary data suggesting that this could be due to Beta-HPV E6s ability to increase BCL6 abundance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2019
- Accession Number
- AD1093488
Entities
People
- Nicholas A Wallace
Organizations
- Kansas State University