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Phosphorylation of ataxin-3 by glycogen synthase kinase 3beta at serine 256 regulates the aggregation of ataxin-3.

Machado-Joseph disease (MJD) is a dominant neurodegenerative disorder caused by an expansion of the polyglutamine tract in MJD-1 gene product, ataxin-3. Recently, studies show that phosphorylation of polyglutamine disease proteins, such as huntingtin, ataxin-1 and DRPLA, plays an important role in regulating pathogenesis. However, the kinase that phosphorylates ataxin-3 remains unknown. Here we show that S256 site in ataxin-3 is phosphorylated by GSK 3beta. Moreover, S256A mutant of expanded ataxin-3 forms high molecular weight protein aggregation, whereas S256D mutant and expanded ataxin-3 without mutation on this site are monomeric. The molecular chaperone Hsp70 represses the aggregation of S256A mutant. Our results imply that phosphorylation of serine 256 in ataxin-3 by GSK 3beta regulates ataxin-3 aggregation.

Pubmed ID: 17434145

Authors

  • Fei E
  • Jia N
  • Zhang T
  • Ma X
  • Wang H
  • Liu C
  • Zhang W
  • Ding L
  • Nukina N
  • Wang G

Journal

Biochemical and biophysical research communications

Publication Data

June 1, 2007

Associated Grants

None

Mesh Terms

  • Binding Sites
  • Cell Line
  • Enzyme Activation
  • Glycogen Synthase Kinase 3
  • Humans
  • Kidney
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Phosphorylation
  • Protein Binding
  • Repressor Proteins
  • Serine