VRK1 functions in the DNA damage and oxidative stress responses and its implication in novel cancer therapies
Elena Navarro Carrasco
Centro de Investigación del Cáncer- IBMCC, Salamanca
VRK1 (Vaccinia-related kinase 1) is a serine/threonine kinase that is mainly present in the nucleus and is expressed in all tissues. Numerous studies demonstrate the critical function of this kinase in a variety of cellular processes including the DNA damage response (DDR), chromatin remodeling, and cell cycle progression. Over the past decades, several VRK1 direct targets have been characterized including transcription factors like p53 and c-Jun, chromatin-related proteins like histone H3 and Tip60, and DDR-related proteins like histone H2AX, 53BP1, and NBS1. Moreover, VRK1 is overexpressed and has been associated with poor prognosis and recurrence in several cancer types such as gliomas, breast, liver, and colon cancer. We investigate VRK1 implication in the DDR and chromatin remodeling, unveiling novel proteins that are regulated by this kinase. In particular, we focus on deciphering VRK1 functions in chromatin remodeling and the DDR induced by current glioblastoma multiforme (GBM) therapies. Additionally, we study VRK1 role as a regulator of chromatin remodeling in the oxidative stress response. Therefore, we propose VRK1 inhibition as an alternative cancer treatment in synthetic lethality strategies.