Human Molecular Genetics, 1999, Vol. 8, No. 9 1657-1664
© 1999 Oxford University Press
Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7
1Institute of Human Genetics, 2Department of Laboratory Medicine and Pathology, 3Department of Neurology and 4Department of Biochemistry, University of Minnesota, Minneapolis, MN 55455, USA
Spinocerebellar ataxia type 7 (SCA7) belongs to a group of neurological disorders caused by a CAG repeat expansion in the coding region of the associated gene. To gain insight into the pathogenesis of SCA7 and possible functions of ataxin-7, we examined the subcellular localization of ataxin-7 in transfected COS-1 cells using SCA7 cDNA clones with different CAG repeat tract lengths. In addition to a diffuse distribution throughout the nucleus, ataxin-7 associated with the nuclear matrix and the nucleolus. The location of the putative SCA7 nuclear localization sequence (NLS) was confirmed by fusing an ataxin-7 fragment with the normally cytoplasmic protein chicken muscle pyruvate kinase. Mutation of this NLS prevented protein from entering the nucleus. Thus, expanded ataxin-7 may carry out its pathogenic effects in the nucleus by altering a matrix-associated nuclear structure and/or by disrupting nucleolar function.
+ Present address: Howard Hughes Medical Institute, Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
§ To whom correspondence should be addressed. Tel: +1 612 625 3647; Fax: +1 612 626 2600; Email: harry{at}lenti.med.umn.edu
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