1 Laboratory of Molecular Neuropathology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
2 Department of Biology, Hefei Teaching College, Hefei 230061, China

Abstract 

Objective 
Machado-Joseph disease (MJD)/Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by an expansion of polyglutamine tract near the C-terminus of the MJD1 gene product, ataxin-3. The precise mechanism of the MJD/SCA3 pathogenesis remains unclear. A growing body of evidence demonstrates that phosphorylation plays an important role in the pathogenesis of many neurodegenerative diseases. However, few kinases are known to phosphorylate ataxin-3. The present study is to explore whether ataxin-3 is a substrate of casein kinase 2 (CK2). 
Methods 
The interaction between ataxin-3 and CK2 was identified by glutathione S-transferase (GST) pull-down assay and co-immunoprecipition assay. The phosphorylation of ataxin-3 by CK2 was measured by in vitro phosphorylation assays. 
Results 
(1) Both wild type and expanded ataxin-3 interacted with CK2α and CK2β in vitro. (2) In 293 cells, both wild type and expanded ataxin-3 interacted with CK2β, but not CK2α. (3) CK2 phosphorylated wild type and expanded ataxin-3. 
Conclusion 
Ataxin-3 is a substrate of protein kinase CK2.

Keywords

Machado-Joseph disease／spinocerebellar ataxia type 3; ataxin-3：casein kinase 2; phosphorylation

[SpringerLink]