Back to Search
Start Over
Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1
- Publication Year :
- 2005
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c9b9e63e6898da22af7a141f71d56ddf