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Tumor Biology

, Volume 36, Issue 8, pp 6067–6074 | Cite as

Cancerous inhibitor of protein phosphatase 2A promotes premature chromosome segregation and aneuploidy in prostate cancer cells through association with shugoshin

  • Rajash Pallai
  • Aishwarya Bhaskar
  • Natalie Barnett-Bernodat
  • Christina Gallo-Ebert
  • Joseph T. NickelsJr.
  • Lyndi M. Rice
Research Article

Abstract

Yeast two-hybrid (Y2H) studies have shown that cancerous Inhibitor of protein phosphatase 2A (CIP2A) interacted with several proteins, including leucine-rich repeat-containing protein 59 (LRRC59), suggesting that CIP2A may interact with the chromosome maintenance protein, shugoshin (Sgol1). We previously showed that LRRC59 interacted with CIP2A, which was required for CIP2A nuclear localization. Thus, we predicted that CIP2A and Sgol1 may also interact. Sgol1 is a nuclear protein that regulates chromosome segregation during cell division via protection of cohesin ring proteins. Here, we demonstrated that Sgol1 and the C-terminus of CIP2A interact in prostate carcinoma cell lines in a protein phosphatase 2A (PP2A)-dependent manner. Moreover, we demonstrated that depletion of CIP2A in PC-3 cells decreases premature chromosome segregation, whereas overexpression of CIP2A in an immortalized prostate cell line increases premature chromosome segregation. Importantly, we further showed that CIP2A depletion decreases the incidence of aneuploidy and stabilizes cohesin complex proteins, while overexpression of CIP2A destabilizes Sgol1. Thus, our findings strongly suggest that CIP2A promotes cell cycle progression, premature chromosome segregation, and aneuploidy, possibly through a novel interaction with Sgol1.

Keywords

CIP2A Shugoshin LRRC59 PP2A Prostate cancer Aneuploidy 

Notes

Acknowledgments

We would like to express our deepest gratitude to Dr. Eli Mordechai and Genesis Biotechnology Group, LLC for the financial support of this work. We also wish to thank Drs. Martin Adelson, Jason Trama, Igor Pechik, and Maria Webb for their intellectual contributions.

Conflicts of interest

All authors are employed by Genesis Biotechnology Group, LLC (GBG), and the work described was funded by GBG.

Supplementary material

13277_2015_3284_MOESM1_ESM.doc (228 kb)
ESM 1 (DOC 228 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Rajash Pallai
    • 1
  • Aishwarya Bhaskar
    • 1
  • Natalie Barnett-Bernodat
    • 2
    • 3
  • Christina Gallo-Ebert
    • 2
  • Joseph T. NickelsJr.
    • 2
  • Lyndi M. Rice
    • 1
  1. 1.Oncoveda, Cancer Signaling and Cell Cycle Team, Medical Diagnostic Laboratories, LLCGenesis Biotechnology Group, LLCHamiltonUSA
  2. 2.Institute of Metabolic DisordersGenesis Biotechnology Group, LLCHamiltonUSA
  3. 3.Femeris, Medical Diagnostic Laboratories, LLCGenesis Biotechnology Group, LLCHamiltonUSA

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