An X11alpha/FSBP complex represses transcription of the GSK3beta gene promoter

Neuroreport. 2010 Aug 4;21(11):761-6. doi: 10.1097/WNR.0b013e32833bfca0.

Abstract

X11alpha is a neuronal adaptor protein that interacts with the amyloid precursor protein (APP) through a centrally located phosphotyrosine binding domain to inhibit the production of Abeta peptide that is deposited in Alzheimer's disease brains. X11alpha also contains two C-terminal postsynaptic density-95, large discs, zona occludens 1 (PDZ) domains, and we show here that through its PDZ domains, X11alpha interacts with a novel transcription factor, fibrinogen silencer binding protein. Moreover, we show that an X11alpha/fibrinogen silencer binding protein complex signals to the nucleus to repress glycogen synthase kinase-3beta promoter activity. Glycogen synthase kinase-3beta is a favoured candidate kinase for phosphorylating tau in Alzheimer's disease. Our findings show a new function for X11alpha that may impact on Alzheimer's disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Animals
  • Blotting, Northern
  • Brain / metabolism*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Gene Expression Regulation / physiology*
  • Glycogen Synthase Kinase 3 / biosynthesis*
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Promoter Regions, Genetic
  • Rats
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • APBA1 protein, human
  • Adaptor Proteins, Signal Transducing
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Transcription Factors
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Glycogen Synthase Kinase 3