Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin‐1
Copyright policy )Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin‐1
Ataxin-1 is a neurodegenerative disorder protein whose glutamine-repeat expanded form causes spinocerebellar ataxia type 1 (SCA1) in humans and exerts cytotoxicity in Drosophila and mouse. We report here that the cytotoxicity caused by ataxin-1 is modulated by association with a related protein, Brother of ataxin-1 (Boat). Boat and ataxin-1 share a conserved AXH (ataxin-1 and HMG-box protein 1) domain, which is essential for both proteins' interactions with the transcriptional corepressor SMRT and its Drosophila homolog, SMRTER. The Boat-ataxin-1 interaction is mediated through multiple regions in both proteins, including a newly identified NBA (N-terminal region of Boat and ataxin-1) domain. We investigated the physiological relevance of the Boat-ataxin-1 interaction in Drosophila and discovered that a mutant ataxin-1-mediated eye defect is suppressed by ataxin-1's association with Boat. Correspondingly, in transgenic SCA1 mouse, Boat expression is greatly reduced in Purkinje cells, the primary targets of SCA1. Our study thus establishes that Boat is an in vivo binding partner of ataxin-1 whose altered expression in Purkinje cells may contribute to their degeneration in SCA1 animals.
- University of California, San Francisco United States
- University of California, San Diego United States
- University of California, San Diego United States
- North Mississippi Medical Center United States
- Rutgers, The State University of New Jersey United States
Cell Nucleus, Gene Expression Profiling, Molecular Sequence Data, Brain, Nuclear Proteins, Nerve Tissue Proteins, Eye, Histone Deacetylases, Cell Line, DNA-Binding Proteins, Mice, Drosophila melanogaster, Ataxins, Gene Expression Regulation, Mutation, Animals, Humans, Nuclear Receptor Co-Repressor 2, Amino Acid Sequence, Ataxin-1
Cell Nucleus, Gene Expression Profiling, Molecular Sequence Data, Brain, Nuclear Proteins, Nerve Tissue Proteins, Eye, Histone Deacetylases, Cell Line, DNA-Binding Proteins, Mice, Drosophila melanogaster, Ataxins, Gene Expression Regulation, Mutation, Animals, Humans, Nuclear Receptor Co-Repressor 2, Amino Acid Sequence, Ataxin-1
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