COPS2 Antagonizes OCT4 to Accelerate the G2/M Transition of Mouse Embryonic Stem Cells

Abstract

Summary: Proper regulation of the cell cycle is essential to safeguard the genomic integrity of embryonic stem cells (ESCs) while maintaining the fast proliferation rate. The pluripotency factor OCT4 has been shown to inhibit CDK1 activation, thus preventing mitotic entry and facilitating the maintenance of genomic integrity. Yet, how ESCs enter mitosis in the presence of OCT4 remains unclear. We previously reported that COPS2 promotes the progression through the G2/M phase of mouse ESCs. In this study, through co-immunoprecipitation and mass spectrometric analysis, we found that COPS2 interacts with OCT4 and CDK1. We further demonstrated that COPS2 stimulates the activity of CDK1/CYCLIN B only when OCT4 is present. Consistently, COPS2 promotes the G2/M transition only in the presence of OCT4 in HeLa cells. Mechanistically, COPS2 attenuates the interaction between OCT4 and CDK1 by sequestering OCT4 and forming a COPS2/CDK1 complex, thus blocking the inhibitory effect of OCT4 on CDK1 activation. : Chen and colleagues identified a unique role of COPS2 in maintaining the short G2/M phase of embryonic stem cells. By competing with OCT4 in binding to CDK1, COPS2 alleviates the inhibitory effect of OCT4 on CDK1 activation, thus allowing the rapid G2/M transition in embryonic stem cells. Keywords: COPS2, OCT4, CDK1, cell cycle, embryonic stem cells