Nuclear localization of the spinocerebellar ataxia type 7 protein, ataxin-7.

Abstract

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.

• Authors: M D Kaytor, L A Duvick, P J Skinner, M D Koob, L P Ranum, H T Orr
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 8 Issue 9 Pg. 1657-64 (Sep 1999) ISSN: 0964-6906 [Print] England
• PMID: 10441328 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATXN7 protein, human
• Ataxin-7
• Neoplasm Proteins
• Nerve Tissue Proteins
• Nuclear Localization Signals
• Nuclear Proteins
• Promyelocytic Leukemia Protein
• Recombinant Fusion Proteins
• Transcription Factors
• Tumor Suppressor Proteins
• PML protein, human
• Pyruvate Kinase

Topics

• Animals
• Ataxin-7
• COS Cells
• Fluorescent Antibody Technique
• Humans
• Neoplasm Proteins (metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Nuclear Localization Signals (genetics)
• Nuclear Matrix (metabolism)
• Nuclear Proteins (metabolism)
• Promyelocytic Leukemia Protein
• Pyruvate Kinase (metabolism)
• Recombinant Fusion Proteins (metabolism)
• Spinocerebellar Ataxias (genetics)
• Transcription Factors (metabolism)
• Transfection
• Tumor Suppressor Proteins