Dephosphorylation of Bcl-2 by protein phosphatase 2A results in apoptosis resistance

Cancer Sci. 2004 Mar;95(3):266-70. doi: 10.1111/j.1349-7006.2004.tb02214.x.

Abstract

The anti-apoptotic protein, Bcl-2 was phosphorylated at the Ser-87 residue in normal human blood cells, while it was not phosphorylated in tumor cells. We identified protein phosphatase 2A (PP2A) as a Bcl-2-associated phosphatase that is responsible for dephosphorylation of Bcl-2 in tumor cell lines. Treatment of the tumor cells with a PP2A inhibitor resulted in the appearance of Bcl-2 phosphorylation at Ser-87. This observation suggests that Bcl-2 is constitutively phosphorylated, but is immediately dephosphorylated by PP2A in tumors. Phosphorylation of Bcl-2 protein at the Ser-87 residue resulted in a reduction in anti-apoptotic function in human tumor cell lines. Thus, not only the expression level, but also the dephosphorylation status may have important implications for the oncogenic activity of Bcl-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Blood Cells / metabolism
  • Blotting, Western
  • Cell Line, Tumor
  • Humans
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Phosphatase 2
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2