title: Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein.
abstract: 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 approximately 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.
authors.affiliation: Department of Genetics, Cell Biology and Development, Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Davidson
authors.forename: B
authors.initials: B
authors.lastname: Riley
authors.forename: E N
authors.initials: EN
authors.lastname: Burright
authors.forename: L A
authors.initials: LA
authors.lastname: Duvick
authors.forename: H Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: H T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D000071183:Autophagy-Related Proteins; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D009928:Organ Specificity; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D014452:Ubiquitins / Q000235:genetics*
chemical_list: C000593749:ATXN1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C486020:UBIN protein, mouse; C405662:UBQLN2 protein, human; C421907:UBQLN4 protein, human; D014452:Ubiquitins