Vande Pol, Scott B.
Associate Professor, Pathology
Biochemistry, Cancer Biology, Cell and Developmental Biology, Microbiology, Molecular Biology
How Viruses, Particularly Papillomaviruses, Can Cause Cancer
Papillomaviruses cause the most common lethal malignancy in women world-wide: cervical cancer. Our laboratory studies the actions of the papillomavirus E6 oncoprotein. By identifying host proteins that associate with E6, we identify those cellular factors that are critical in signal transduction and cell cycle progression. We use a variety of biochemical and genetic approaches to identify the cellular targets of E6, and then we study the consequences of the interaction and the role of the cellular protein in cancer. E6 targets we have identified include:
Paxillin is a critical adapter molecule involved in the regulation of integrin signaling, and the activation of tyrosine kinase signaling pathways. Ongoing studies are directed at understanding the mechanism by which paxillin activates Focal Adhesion Kinase, and the role of paxillin in cancer.
PTPN3 and PTPN4. We recently discovered that E6 interacts with the tyrosine phosphatases PTPN3 and PTPN4, and then catalyze their degradation in living cells. Tyrosine phosphatases are critical regulators of signal transduction and cell proliferation. We seek to understand how the loss of PTPN3 and PTPN4 serves the viral life cycle and may promote cancer.
PDZ proteins that regulate polarity and signal transduction. E6 interacts with a set of cellular proteins that contain PDZ domains. This interaction is essential for E6 to promote cancer. We seek to understand which of the E6-PDZ interactions are critical for E6 to promote cancer and how these PDZ domain proteins prevent cancer.
A second area of research concerns determining the structure of E6 . E6 structure has frustrated laboratories worldwide for 20 years because the protein is insoluble. We have recently identified new techniques to make soluble E6 proteins, and are engaged in an international collaboration to solve the structure of E6 by NMR.
Potential Rotation Projects: 1. Identify new targets of Papillomavirus oncoproteins that have unknown transformation mechanisms 2. Determine if the degradation of cellular targets by E6 is regulated by cellular signaling 3. Examine the interaction of PTPH1 with novel tyrosine phosphorylated substrates. 4. Express novel E6 proteins for structural analysis.