Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein

J. D. Davidson, B. Riley, E. N. Burright, L. A. Duvick, H. Y. Zoghbi, H. T. Orr
2000 Human Molecular Genetics  
Expansion of a polyglutamine tract within ataxin-1 causes spinocerebellar ataxia type 1 (SCA1). In this study, we used the yeast two-hybrid system to identify an ataxin-1-interacting protein, A1Up. A1Up localized to the nucleus and cytoplasm of transfected COS-1 cells. In the nucleus, A1Up co-localized with mutant ataxin-1, further demonstrating that A1Up interacts with ataxin-1. Expression analyses demonstrated that A1U mRNA is widely expressed as an ∼4.0 kb transcript and is present in
more » ... s present in Purkinje cells, the primary site of SCA1 cerebellar pathology. Sequence comparisons revealed that A1Up contains an Nterminal ubiquitin-like (UbL) region, placing it within a large family of similar proteins. In addition, A1Up has substantial homology to human Chap1/Dsk2, a protein that binds the ATPase domain of the HSP70like Stch protein. These results suggest that A1Up may link ataxin-1 with the chaperone and ubiquitinproteasome pathways. In addition, these data support the concept that ataxin-1 may function in the formation and regulation of multimeric protein complexes within the nucleus.
doi:10.1093/oxfordjournals.hmg.a018922 pmid:11001934 fatcat:bl4v6k7cmvfwxpekjmebr6xkwi