Ubiquitin Signaling in Ovarian Cancer: From Potential to Challenges

Abstract

Ubiquitin proteasome system (UPS) is an emerging arena in cancer intervention. Dysregulation of various UPS components has been implicated with many cancers, and this knowledge is starting to be exploited for its role in cancer initiation, progression, and therapeutics. UPS regulates both protein turnover and non-proteolytic regulatory function of the proteins involved in cell cycle, signal transduction, DNA repair, histone modi- fication, and transcription. In addition, chromosomal aberrations and genomic alterations often present in the cancer cell genomes lead to excess of conformationally challenged aggregation-prone proteins and proteotoxic stress that make cancer cells more dependent on UPS-mediated protein degradation than normal cells. This proposition is the basis of the clinical use of proteasome inhibitor, Bortezomib, to treat multiple myeloma and mantle cell lymphoma targeting cancer cells and mostly sparing the normal cells. This chapter provides an overview of various components of UPS which are implicated in cancer and regulate ubiquitin-mediated oncogenic signaling in ovarian cancer.