β-TRCP-mediated AEBP2 ubiquitination and destruction controls cisplatin resistance in ovarian cancer

Abstract

AEBP2 is a zinc finger protein and a potential targeting protein for the mammalian Polycomb Repression Complex 2 (PRC2). The role of AEBP2 in the regulation of the migration and development of the neural crest cells through the PRC2-mediated epigenetic mechanism has been well-documented. However, whether AEBP2 plays a role in cancer and how to regulate AEBP2 itself remains largely unknown. Here, we show that genetic knockout of AEBP2 inhibited ovarian cancer cells proliferation and increased cisplatin sensitivity. Moreover, AEBP2 contains a non-canonical phosphodegron and is constantly targeted for ubiquitylation and proteasomal degradation by a SKP1–CUL1–F-box protein (SCF) β-TrCP ubiquitin ligase complex. Failure to degrade AEBP2 conferred cisplatin resistance in ovarian cancer. Overall, this study reveals an oncogenic role of AEBP2 in ovarian cancer and provides a rationale to target β-TRCP-AEBP2 axis in ovarian cancer that may be therapeutically beneficial.