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

Stem Cell Reports. 2018 Aug 14;11(2):317-324. doi: 10.1016/j.stemcr.2018.06.013. Epub 2018 Jul 19.

Abstract

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.

Keywords: CDK1; COPS2; OCT4; cell cycle; embryonic stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism
  • COP9 Signalosome Complex / metabolism*
  • G2 Phase Cell Cycle Checkpoints*
  • Gene Knockdown Techniques
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism*
  • Nuclear Proteins / metabolism*
  • Octamer Transcription Factor-3 / antagonists & inhibitors*
  • Octamer Transcription Factor-3 / metabolism
  • Protein Binding
  • Transcription Factors / metabolism*

Substances

  • Cops2 protein, mouse
  • Nuclear Proteins
  • Octamer Transcription Factor-3
  • Pou5f1 protein, mouse
  • Transcription Factors
  • CDC2 Protein Kinase
  • Cdk1 protein, mouse
  • COP9 Signalosome Complex