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| Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract |
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| Author(s): Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, Bromm M, KazemiEsfarjani P, Thornberry NA, Vaillancourt JP, Hayden MR |
| Source: NATURE GENETICS Volume: 13 Issue: 4 Pages: 442-449 Published: AUG 1996 |
| Times Cited: 383 References: 37 |
| Abstract: Apoptosis has recently been recognized as a mode of cell death in Huntington disease (HD). Apopain, a human counterpart of the nematode cysteine protease death-gene product, CED-3, has a key role in proteolytic events leading to apoptosis. Here we show that apoptotic extracts and apopain itself specifically cleave the HD gene product, huntingtin. The rate of cleavage increases with the length of the huntingtin polyglutamine tract, providing an explanation for the gain-of-function associated with CAG expansion. Our results show that huntingtin is cleaved by cysteine proteases and suggest that HD might be a disorder of inappropriate apoptosis. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV BRITISH COLUMBIA, DEPT MED GENET, VANCOUVER, BC CANADA
2. MERCK FROSST CTR THERAPEUT RES, DEPT BIOCHEM & MOL BIOL, MONTREAL, PQ CANADA
3. MERCK & CO INC, MERCK SHARP & DOHME RES LABS, DEPT ENZYMOL, RAHWAY, NJ 07065 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Genetics & Heredity |
| IDS Number: VB620 |
| ISSN: 1061-4036 |
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