Super resoulution microscopies applied to the study of tirosin kinase 2 (PTK2) and miosin V family roles in the DNA damage response in cardiomiocites under genotoxic stress

Abstract

Cardiovascular complications of anticancer therapies have emerged as a critical problem in public health, especially if we consider that cancer survival rate is increasing in the last years. Cardiotoxicity due to chemotherapy, like treatment with doxorubicin (doxo), is a serious condition, which can evolve to chronic cardiopathy leading to death. Studies focused on signaling activated by anticancer therapies have been showing an important role of the protein tyrosine kinase 2 (PTK2) in the cellular survival and resistance, however, this signaling is not well understood. This research proposal aims to investigate the molecular basis of this cellular resistance and survival, by verifying the interaction between PTK2 with proteins associated with DNA damage response, such as PARP1 and MRE11. It is also our objective to elucidate the transport mechanism of PTK2 in the cytoplasm and nucleus and to verify the role of the molecular motor family of myosins V in the DNA damage response. Our results could contribute to the understanding of the mechanisms in which PTK2 promotes cellular survival after doxo treatment and to the establishment of new treatments to cancer with decreasing deleterious effects to the cardiac function. (AU)