Oncogenic Fusion Proteins and the Centrosome

Myeloproliferative disorders (MPD) are a type of leukemia that results in the abnormal expansion of myeloid stem cells. Chromosomal translocations are common in MPD and result in gene fusions between receptor tyrosine kinases and partner proteins. The resulting fusion is an oncogene that drives proliferation and survival in these cancers. While the importance of the partner protein is still unclear, many of these proteins normally localize to the centrosome.  As the centrosome is important for cell cycle progression and provides a discrete location within the cell, it is possible that centrosome localization confers properties upon the fusions that contribute to their oncogenic character.  My project is to determine the localization of the oncogenic fusion proteins: coiled- coil containing domain protein 6 (CCDC6)- platelet derived growth factor (PDGFR), huntingtin interacting protein 1 (HIP1)-(PDGFR), and zinc finger 198 (ZNF198)- fibroblast growth factor receptor 1 (FGFR1). In this project, we will construct expression vectors containing the respective fusions and look for their centrosome localization in mouse embryonic fibroblast (MEF) and retinal pigment epithelial RPE-1) cells. Through this project, we hope to better understand these myeloproliferative fusions specifically and determine the mechanism that favors centrosomally-localized proteins as fusion partners.