Mechanism of inhibition of PP2A activity and abnormal hyperphosphorylation of tau by I2(PP2A)/SET

FEBS Lett. 2011 Sep 2;585(17):2653-9. doi: 10.1016/j.febslet.2011.07.020. Epub 2011 Jul 28.

Abstract

Protein phosphatase-2A (PP2A) activity, which is compromised in Alzheimer disease brain, is regulated by two endogenous inhibitors, one of them being I(2)(PP2A), a 277 amino acid long protein also known as SET. Here we report that both the amino terminal fragment (I(2NTF); aa 1-175) and the carboxy terminal fragment (I(2CTF); aa 176-277) of I(2)(PP2A) inhibit PP2A by binding to its catalytic subunit PP2Ac and cause hyperphosphorylation of tau. The C-terminal acidic region in I(2CTF) and Val 92 in I(2NTF) are essential for their association with PP2Ac and inhibition of the phosphatase activity.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • DNA-Binding Proteins
  • Histone Chaperones / metabolism*
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Phosphorylation
  • Protein Binding
  • Protein Phosphatase 2 / metabolism*
  • Protein Subunits
  • Transcription Factors / metabolism*
  • tau Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • Histone Chaperones
  • Protein Subunits
  • SET protein, human
  • Transcription Factors
  • tau Proteins
  • Protein Phosphatase 2