COPS5 inhibition arrests the proliferation and growth of serous ovarian cancer cells via the elevation of p27 level

Biochem Biophys Res Commun. 2017 Nov 4;493(1):85-93. doi: 10.1016/j.bbrc.2017.09.070. Epub 2017 Sep 15.


The fifth component of the COP9 signalosome complex (COPS5), which plays an essential role in ubiquitin-mediated protein degradation, has been found as a prognostic biomarker for multiple cancers, however, the role of COPS5 in serous ovarian cancer (SOC) remain to be clarified. In this study, we found that COPS5 expression was significantly increased in SOC cells and tissues compared with those controls. Mechanistically, COPS5 and p27was proved to interact with each other, with COPS5 acts as a negative regulator of p27. SOC cells with COPS5 depletion were arrested in G1/G0-phase and exhibited a reduced proliferation ability and an increased cytoplasmic p27 expression. Whereas, the cells were stuck at S-phase accompanied with an elevation of nucleus p27 expression after knocking down COPS6 or blocking COPS5 by CSN5i-3. Furthermore, inhibition of COPS5 resulted in an elevation of Akt expression and sensitized SOC cells to Akt inhibitor MK2206. Suppression of COPS5 and Akt offers a potential strategy for the treatment of SOC.

Keywords: Akt; COPS5; COPS6; Serous ovarian cancer; p27.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COP9 Signalosome Complex
  • Cell Cycle Checkpoints
  • Cell Proliferation*
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cystadenocarcinoma, Serous / metabolism*
  • Cystadenocarcinoma, Serous / pathology*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Peptide Hydrolases / metabolism*
  • Tumor Cells, Cultured


  • Intracellular Signaling Peptides and Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex