Article
- The EMBO Journal (2005) 24, 3339 - 3351
- doi:10.1038/sj.emboj.7600785
Published online: 25 August 2005
Subject Categories:
Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1
Akifumi Mizutani1,a, Lei Wang1, Harini Rajan1, Parminder JS Vig2, William A Alaynick3,4, Joshua P Thaler3,4 and Chih-Cheng Tsai1
- Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA
- Department of Neurology, The Mississippi Medical Center, Jackson, MS, USA
- Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA
- Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA
Correspondence to:
Chih-Cheng Tsai, Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 683 Hoes Lane, Room 163, Piscataway, NJ 08854, USA. Tel.: + 1 732 235 4885; Fax: +1 732 235 5823; E-mail: tsaich@umdnj.edu
aPresent address: Division of Development and Differentiation, National Institute of Neuroscience, 4-1-1 Ogawahigashi-machi, Kodaira, Tokyo 187-8502, Japan
Received 19 January 2005; Accepted 22 July 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.
Keywords:
- ataxin-1,
- Boat,
- SCA1,
- SMRT,
- SMRTER
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