Human Molecular Genetics, 2000, Vol. 9, No. 15 2305-2312
© 2000 Oxford University Press
Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein
1Department of Genetics, Cell Biology and Development, 2Department of Laboratory Medicine and Pathology, 3Department of Biochemistry, Molecular Biology and Biophysics, and 4Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA, and 5Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
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 Purkinje cells, the primary site of SCA1 cerebellar pathology. Sequence comparisons revealed that A1Up contains an N-terminal 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 HSP70-like Stch protein. These results suggest that A1Up may link ataxin-1 with the chaperone and ubiquitin–proteasome 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.
+ To whom correspondence should be addressed. Tel: +1 612 625 3647; Fax: +1 612 626 2600; Email: harry@lenti.med.umn.edu
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