Deciphering of Cellular Signaling Pathways Using Polyomaviruses

The Gjoerup lab focuses on studying polyomavirus oncoproteins to gain insight to cellular mechanisms. This includes investigations of mouse polyoma large T (LT), and SV40 LT, antigens in regulation of viral DNA replication, as well as contributions of SV40 LT and small t antigen in oncogenic transformation and cell death pathways, respectively. We have also collaboratively studied the Merkel cell polyomavirus LT and identified a novel, unique interactor by tandem affinity purification.

We were the first to identify the Bub1 mitotic checkpoint kinase as a novel interactor of SV40 LT. Our LT mutant analysis first linked Bub1 binding to viral transformation and spindle checkpoint dysfunction. We also revealed an important link between Bub1 loss and the p53 checkpoint response in normal cells. Our analysis has connected LT/ Bub1 binding with induction of both tetraploidy and the DNA damage response.

Our goal is to continue to use the polyomavirus T antigens as model systems to understand fundamental cellular mechanisms, primarily those involved with guarding genome integrity and preventing tumorigenesis. We remain focused on using the SV40 toolbox to elucidate novel players and mechanisms relevant for understanding the interplay between DNA damage responses, repair, checkpoints and malignant transformation.