FAM122A, a new endogenous inhibitor of protein phosphatase 2A

Oncotarget. 2016 Sep 27;7(39):63887-63900. doi: 10.18632/oncotarget.11698.

Abstract

The regulation of the ubiquitously expressed protein phosphatase 2A (PP2A) is essential for various cellular functions such as cell proliferation, transformation, and fate determination. In this study, we demonstrate that the highly conserved protein in mammals, designated FAM122A, directly interacts with PP2A-Aα and B55α rather than B56α subunits, and inhibits the phosphatase activity of PP2A-Aα/B55α/Cα complex. Further, FAM122A potentiates the degradation of catalytic subunit PP2A-Cα with the increased poly-ubiquitination. In agreement, FAM122A silencing inhibits while its overexpression enhances cell growth and colony-forming ability. Collectively, we identify FAM122A as a new endogenous PP2A inhibitor and its physiological and pathophysiological significances warrant to be further investigated.

Keywords: FAM122A; PP2A; cell growth; phosphatase activity; ubiquitination.

MeSH terms

  • A549 Cells
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Proliferation
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation, Neoplastic*
  • Gene Silencing
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Phosphatase 2 / antagonists & inhibitors*
  • Protein Phosphatase 2 / metabolism
  • Protein Phosphatase 2C / metabolism
  • Protein Processing, Post-Translational
  • Protein Subunits / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism
  • Ubiquitination

Substances

  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • PABIR1 protein, human
  • Phosphoproteins
  • Protein Subunits
  • Protein Phosphatase 2
  • Protein Phosphatase 2C
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2