کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1937622 | 1050721 | 2007 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Phosphorylation of ataxin-3 by glycogen synthase kinase 3β at serine 256 regulates the aggregation of ataxin-3 Phosphorylation of ataxin-3 by glycogen synthase kinase 3β at serine 256 regulates the aggregation of ataxin-3](/preview/png/1937622.png)
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 3β. 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 3β regulates ataxin-3 aggregation.
Journal: Biochemical and Biophysical Research Communications - Volume 357, Issue 2, 1 June 2007, Pages 487–492