Human papillomaviruses (HPV) are a family of diverse double-stranded DNA viruses. Over 200 HPV genotypes have been identified. HPVs are classified as high-risk (cancer-causing) or low-risk (not cancer-causing). Viral proteins encoded by the high-risk HPV genome can lead to cell transformation and cancer. One of the main carcinogenic proteins in my project is E7.

E7 has two main functions in the cell. One of the carcinogenic activities of high-risk HPV E7 is to bind and degrade the retinoblastoma protein (RB1), allowing passage through the G1/S checkpoint of the cell cycle. E7 binding to RB is necessary but insufficient for transformation. Our lab is testing the hypothesis that E7 must also bind and degrade the tumor suppressor PTPN14 to promote cell growth. Different HPV E7 proteins reduce PTPN14 levels to different extents. 

The goal of my project is to measure the binding affinity of PTPN14 to different HPV E7 proteins and test whether there is a correlation between binding affinity and PTPN14 levels. There is no current data on the relationship between binding affinity and degradation. If a correlation was found between the two, then that would give an indication for why high-risk HPV E7s degrade better than low-risk ones. 

Current methods of protein growth and purification are outlined. Future studies will include working with surface plasmon resonance (SPR) to quantitatively measure the binding affinities of PTPN14 and E7 and establishing whether there is a correlation or not.