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

Jennifer D. Davidson, Brigit Riley, Eric N. Burright, Lisa A. Duvick, Huda Y. Zoghbi, Harry T. Orr

Research output: Contribution to journalArticlepeer-review

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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 ~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.

Original languageEnglish (US)
Pages (from-to)2305-2312
Number of pages8
JournalHuman molecular genetics
Volume9
Issue number15
DOIs
StatePublished - Sep 22 2000

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