Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1
| Autor: | Joshua P. Thaler, Akifumi Mizutani, Lei Wang, Harini Rajan, William A. Alaynick, Chih-Cheng Tsai, Parminder J.S. Vig |
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| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Transcription
Genetic Mutant Protein domain Molecular Sequence Data Ataxin 1 Nerve Tissue Proteins Plasma protein binding Eye DNA-binding protein General Biochemistry Genetics and Molecular Biology Article Histone Deacetylases Cell Line Mice Animals Humans Nuclear Receptor Co-Repressor 2 Amino Acid Sequence Nuclear protein Molecular Biology Ataxin-1 Regulation of gene expression Cell Nucleus General Immunology and Microbiology biology General Neuroscience Gene Expression Profiling fungi Brain Nuclear Proteins biology.organism_classification Molecular biology Protein Structure Tertiary body regions DNA-Binding Proteins Repressor Proteins Drosophila melanogaster Phenotype Ataxins Gene Expression Regulation Mutation biology.protein Sequence Alignment Protein Binding |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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