All roads lead to PP2A: exploiting the therapeutic potential of this phosphatase

FEBS J. 2016 Mar;283(6):1004-24. doi: 10.1111/febs.13573. Epub 2015 Nov 14.


Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase involved in the regulation of many cellular processes. A confirmed tumor suppressor protein, PP2A is genetically altered or functionally inactivated in many cancers highlighting a need for its therapeutic reactivation. In this review we discuss recent literature on PP2A: the elucidation of its structure and the functions of its subunits, and the identification of molecular lesions and post-translational modifications leading to its dysregulation in cancer. A final section will discuss the proteins and small molecules that modulate PP2A and how these might be used to target dysregulated forms of PP2A to treat cancers and other diseases.

Keywords: CIP2A; PP2A; SET; cancer; cancer biology; cell signaling; drug development; protein phosphatases; structural biology; tumor suppressors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Catalytic Domain
  • Enzyme Inhibitors / pharmacology
  • Gene Deletion
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Models, Molecular
  • Mutation
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / therapy
  • Phosphorylation
  • Protein Phosphatase 2 / chemistry*
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism*
  • Protein Processing, Post-Translational
  • Protein Subunits
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism


  • Enzyme Inhibitors
  • Protein Subunits
  • Tumor Suppressor Proteins
  • Protein Phosphatase 2