USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product.

Abstract

Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder characterized by ataxia and progressive motor deterioration. SCA1 has been known to associate with elongated polyglutamine tract in ataxin-1, the SCA1 gene product. Using the yeast two-hybrid system, we have found that USP7, a ubiquitin-specific protease, binds to ataxin-1. Further experiments with deletion mutants indicated that the C-terminal region of ataxin-1 was essential for the interaction. Liquid beta-galactosidase assay and coimmunoprecipitation experiments revealed that the strength of the interaction between USP7 and ataxin-1 is influenced by the length of the polyglutamine tract in the ataxin-1; weaker interaction was observed in mutant ataxin-1 with longer polyglutamine tract and USP7 was not recruited to the mutant ataxin-1 aggregates in the Purkinje cells of SCA1 transgenic mice. Our results suggest that altered function of the ubiquitin system can be involved in the pathogenesis of spinocerebellar ataxia type 1.

• Authors: Sunghoi Hong, Sung-Jo Kim, Sojeong Ka, Inho Choi, Seongman Kang
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 20 Issue 2 Pg. 298-306 (Jun 2002) ISSN: 1044-7431 [Print] United States
• PMID: 12093161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2002 Elsevier Science (USA).

Chemical References

• ATXN1 protein, human
• Ataxin-1
• Ataxins
• Atxn1 protein, mouse
• Nerve Tissue Proteins
• Nuclear Proteins
• Peptides
• polyglutamine
• Endopeptidases
• USP7 protein, human
• Ubiquitin Thiolesterase
• Ubiquitin-Specific Peptidase 7
• Ubiquitin-Specific Proteases
• Usp7 protein, mouse

Topics

• Animals
• Ataxin-1
• Ataxins
• COS Cells
• Cerebellum (abnormalities, metabolism, pathology)
• Endopeptidases (genetics, isolation & purification, metabolism)
• Immunohistochemistry
• Inclusion Bodies (metabolism, pathology)
• Mice
• Mice, Transgenic
• Mutation (genetics)
• Nerve Tissue Proteins (genetics, metabolism)
• Neurons (metabolism, pathology)
• Nuclear Proteins (genetics, metabolism)
• Peptides (metabolism)
• Protein Binding (physiology)
• Purkinje Cells (metabolism, pathology)
• Spinocerebellar Ataxias (enzymology, genetics, physiopathology)
• Trinucleotide Repeat Expansion (genetics)
• Two-Hybrid System Techniques
• Ubiquitin Thiolesterase
• Ubiquitin-Specific Peptidase 7
• Ubiquitin-Specific Proteases