A huntingtin-associated protein enriched in brain with implications for pathology

Xiao Jiang Li, Shi Hua Li, Alan H. Sharp, Frederick C. Nucifora, Gabriele Schilling, Anthony Lanahan, Paul Worley, Solomon H. Snydert, Christopher A. Ross

Research output: Contribution to journalArticle

Abstract

HUNTINGTON’s disease (HD) is an autosomal dominant neuro-degenerative disorder caused by an expanding polyglutamine repeat in the IT 15 or huntingtin gene1. Although this gene is widely expressed2–9and is required for normal development10–12, the pathology of HD is restricted to the brain, for reasons that remain poorly understood. The huntingtin gene product is expressed at similar levels in patients and controls, and the genetics of the disorder13,14suggest that the expansion of the polyglutamine repeat induces a toxic gain of function, perhaps through interactions with other cellular proteins15–18. Here we report the identification of a protein (huntingtin-associated protein (HAP)-l) that binds to huntingtin. This binding is enhanced by an expanded polyglutamine repeat, the length of which is also known to correlate with the age of disease onset19–21. The HAP-1 protein is enriched in the brain, suggesting a possible basis for the selective brain pathology of HD.

Original languageEnglish (US)
Pages (from-to)398-402
Number of pages5
JournalNature
Volume378
Issue number6555
DOIs
StatePublished - Nov 23 1995

ASJC Scopus subject areas

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