Leucine-rich repeat-containing protein 59 mediates nuclear import of cancerous inhibitor of PP2A in prostate cancer cells

Tumour Biol. 2015 Aug;36(8):6383-90. doi: 10.1007/s13277-015-3326-1. Epub 2015 Apr 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / biosynthesis
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Molecular Targeted Therapy
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Protein Phosphatase 2 / antagonists & inhibitors
  • Protein Phosphatase 2 / metabolism


  • Autoantigens
  • CIP2A protein, human
  • Intracellular Signaling Peptides and Proteins
  • LRRC59 protein, human
  • Membrane Proteins
  • PPP2CA protein, human
  • Protein Phosphatase 2