John C. Wilkinson
Biochemisty of Cancer
Cancer develops when cells lose control of normal biochemical processes. My laboratory is examining how two such processes, cellular metabolism and the intrinsic cellular suicide program known as apoptosis, contribute to the pathogenesis of cancer and other human diseases. We are currently focused on the study of two factors, apoptosis inducing factor (AIF) and its associated factor phosphoglycerate mutase family member 5 (PGAM5). These molecules directly regulate the apoptotic process, but also possess signaling properties that are distinct from their roles during cell death. AIF promotes cell death by caspase independent means, but we have also discovered that AIF promotes prostate cancer progression by regulating mitochondrial energy production. PGAM5 helps promote survival through regulating cellular antioxidant defenses, yet paradoxically appears to promote cell death under certain conditions through a novel mechanism. Our research efforts are currently focused on evaluating the roles of AIF and PGAM5 in promoting the process of tumorigenesis. We address our research questions by utilizing a variety of techniques spanning the disciplines of molecular biology, biochemistry, and in vivo tumor biology.
Lewis, E. M., Wilkinson, A. S., Jackson, J. S., Mehra, R., Varambally, S., Chinnaiyan, A. M., and Wilkinson, J. C. (2012) The Enzymatic Activity of Apoptosis Inducing Factor Supports Energy Metabolism Benefitting the Growth and Invasiveness of Advanced Prostate Cancer Cells. The Journal of Biological Chemistry 287(52), 43862-43875.
Lewis, E. M., Wilkinson, A. S., Davis, N. Y., Horita, D. A., and Wilkinson, J. C. (2011) Nondegradative ubiquitination of apoptosis inducing factor (AIF) by X-linked inhibitor of apoptosis at a residue critical for AIF-mediated chromatin degradation. Biochemistry, 50 (51), 11084-11096.
Topping, R. P., Wilkinson, J. C., and Scarpinato, K. D. (2009) Mismatch repair protein deficiency compromises cisplatin-induced apoptotic signaling. The Journal of Biological Chemistry 284 (21), 14029-14039.
Wilkinson, J. C., Wilkinson, A. S., Galbán, S., Csomos, R. A., and Duckett, C. S. (2008) Apoptosis inducing factor is a target for ubiquitination through interaction with XIAP. Molecular and Cellular Biology 28(1), 237-247.