TY - JOUR
T1 - Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract
AU - Wellington, Cheryl L.
AU - Ellerby, Lisa M.
AU - Hackam, Abigail S.
AU - Margolis, Russell L.
AU - Trifiro, Mark A.
AU - Singaraja, Roshni
AU - McCutcheon, Krista
AU - Salvesen, Guy S.
AU - Propp, Stephanie S.
AU - Bromm, Michael
AU - Rowland, Kathleen J.
AU - Zhang, Taiqi
AU - Rasper, Dita
AU - Roy, Sophie
AU - Thornberry, Nancy
AU - Pinsky, Leonard
AU - Kakizuka, Akira
AU - Ross, Christopher A.
AU - Nicholson, Donald W.
AU - Bredesen, Dale E.
AU - Hayden, Michael R.
PY - 1998/4/10
Y1 - 1998/4/10
N2 - The neurodegenerative disease Huntington disease, dentatorubropallidoluysian atrophy, spinocerebellar atrophy type 3, and spinal bulbar muscular atrophy are caused by expansion of a polyglutamine tract within their respective gene products. There is increasing evidence that generation of truncated proteins containing an expanded polyglutamine tract may be a key step in the pathogenesis of these disorders. We now report that, similar to huntingtin, atrophin-1, ataxin-3, and the androgen receptor are cleaved in a apoptotic extracts. Furthermore, each of these proteins is cleaved by one or more purified caspases, cysteine proteases involved in apoptotic death. The CAG length does not modulate susceptibility to cleavage of any of the full-length proteins. Our results suggest that by generation of truncated polyglutamine-containing proteins, caspase cleavage may represent a common step in the pathogenesis of each of these neurodegenerative diseases.
AB - The neurodegenerative disease Huntington disease, dentatorubropallidoluysian atrophy, spinocerebellar atrophy type 3, and spinal bulbar muscular atrophy are caused by expansion of a polyglutamine tract within their respective gene products. There is increasing evidence that generation of truncated proteins containing an expanded polyglutamine tract may be a key step in the pathogenesis of these disorders. We now report that, similar to huntingtin, atrophin-1, ataxin-3, and the androgen receptor are cleaved in a apoptotic extracts. Furthermore, each of these proteins is cleaved by one or more purified caspases, cysteine proteases involved in apoptotic death. The CAG length does not modulate susceptibility to cleavage of any of the full-length proteins. Our results suggest that by generation of truncated polyglutamine-containing proteins, caspase cleavage may represent a common step in the pathogenesis of each of these neurodegenerative diseases.
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U2 - 10.1074/jbc.273.15.9158
DO - 10.1074/jbc.273.15.9158
M3 - Article
C2 - 9535906
AN - SCOPUS:0032502715
VL - 273
SP - 9158
EP - 9167
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 15
ER -