Abstract
Using yeast two-hybrid analysis, we identified several novel protein interactions for the oncoprotein Cancerous Inhibitor of PP2A (CIP2A) and confirmed a subset of these interactions in human cancer cell lines. Analysis of the interaction in prostate carcinoma cells between CIP2A and leucine-rich repeat-containing protein 59 (LRRC59) suggests that CIP2A is translocated into the nucleus at G2/M through its association with LRRC59. Recent work by others has demonstrated that nuclear CIP2A disrupts mitotic checkpoints, which promotes deregulation of the cell cycle and increases cancerous phenotypes. Thus, we provide a novel therapeutic mechanism for inhibiting CIP2A function in cancerous cells via targeting the CIP2A-LRRC59 interaction.
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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 intellectual contributions to this work and Diana Savoly, Amy Werda, Jamie Francisco for their aid in these studies.
Conflicts of interest
All authors are employed by Genesis Biotechnology Group, LLC (GBG), and the work described was funded by GBG.
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Pallai, R., Bhaskar, A., Barnett-Bernodat, N. et al. Leucine-rich repeat-containing protein 59 mediates nuclear import of cancerous inhibitor of PP2A in prostate cancer cells. Tumor Biol. 36, 6383–6390 (2015). https://doi.org/10.1007/s13277-015-3326-1
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DOI: https://doi.org/10.1007/s13277-015-3326-1