Nature Medicine
2, 347 - 350 (1996)
doi:10.1038/nm0396-347
Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDHJames R. Burke1, 5, 8, Jan J. Enghild2, Margaret E. Martin1, 5, Yuh-Shan Jou6, Richard M. Myers6, Allen D. Roses1, 3, 5, Jeffery M. Vance1, 4, 5, 7
& Warren J. Strittmatter1, 3, 5, 7
1Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 27710, USA
2Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA
3Department of Neurobioiogy, Duke University Medical Center, Durham, North Carolina 27710, USA
4Department of Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA
5Deane Laboratory, Duke University Medical Center, Durham, North Carolina 27710, USA
6Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA
7J.M.V and W.J.S. contributed equally to this work.
8Correspondence should be addressed to J.R.B. At least five adult−onset neurodegenerative diseases, including Huntington disease (HD), and dentatorubral−pallidoluysian atrophy (DRPLA) are produced by genes containing a variably increased CAC repeat within the coding region1−4. The size range of the repeats is similar in all diseases; unaffected individuals have fewer than 30 CAG repeats, whereas affected patients usually have more than 40 repeats. The size of the inherited CAG repeat correlates with the severity and age of disease onset1,5−7. The CAG triplet repeat produces a polyglutamine domain in the expressed proteins3,8−10. All of these diseases are inherited in a dominant fashion, and a pathologic gain of function in gene carriers has been proposed. We sought to identify proteins in the brain that selectively interact with polyglutamine−domain proteins, hypothesizing that the polyglutamine domain may determine protein−protein interactions.
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