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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Ataxin-1
-
Ataxins
-
Brain / metabolism
-
Cell Line
-
Cell Nucleus / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Drosophila melanogaster / genetics
-
Drosophila melanogaster / metabolism
-
Eye / metabolism
-
Gene Expression Profiling
-
Gene Expression Regulation
-
Histone Deacetylases / metabolism
-
Humans
-
Mice
-
Molecular Sequence Data
-
Mutation / genetics*
-
Nerve Tissue Proteins / antagonists & inhibitors*
-
Nerve Tissue Proteins / chemistry
-
Nerve Tissue Proteins / metabolism
-
Nerve Tissue Proteins / toxicity*
-
Nuclear Proteins / antagonists & inhibitors*
-
Nuclear Proteins / chemistry
-
Nuclear Proteins / metabolism
-
Nuclear Proteins / toxicity*
-
Nuclear Receptor Co-Repressor 2
-
Phenotype
-
Protein Binding
-
Protein Structure, Tertiary
-
Repressor Proteins / chemistry
-
Repressor Proteins / genetics
-
Repressor Proteins / metabolism*
-
Sequence Alignment
-
Transcription, Genetic / genetics
Substances
-
ATXN1 protein, human
-
ATXN1L protein, human
-
Ataxin-1
-
Ataxins
-
Atxn1 protein, mouse
-
Atxn1l protein, mouse
-
DNA-Binding Proteins
-
NCOR2 protein, human
-
Ncor2 protein, mouse
-
Nerve Tissue Proteins
-
Nuclear Proteins
-
Nuclear Receptor Co-Repressor 2
-
Repressor Proteins
-
Histone Deacetylases
-
histone deacetylase 3