Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH

• Published in: Nature medicine Vol. 2; no. 3; p. 347
• Main Authors: Burke, J R, Enghild, J J, Martin, M E, Jou, Y S, Myers, R M, Roses, A D, Vance, J M, Strittmatter, W J
• Format: Journal Article
• Language: English
• Published: United States 01.03.1996
• Subjects: Adult; Amino Acid Sequence; Animals; Binding Sites; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; Humans; Huntingtin Protein; Huntington Disease - genetics; Huntington Disease - metabolism; In Vitro Techniques; Minisatellite Repeats; Molecular Sequence Data; Nerve Tissue Proteins - metabolism; Nervous System Diseases - genetics; Nervous System Diseases - metabolism; Nuclear Proteins - metabolism; Protein Binding; Rabbits; Trinucleotide Repeats
• ISSN: 1078-8956
• DOI: 10.1038/nm0396-347

At least five adult-onset neurodegenerative diseases, including Huntingtin disease (HD), and dentatorubral-pallidoluysian atrophy (DRPLA) are produced by genes containing a variably increased CAG repeat within the coding region. 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 onset. The CAG triplet repeat produces a polyglutamine domain in the expressed proteins. 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.