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.
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
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
Biochem. Biophys. Res. Commun.
Date: Jun. 01, 2007
PubMed ID: 17434145
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