SH3GL3 associates with the huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates

被引:179
作者
Sittler, A
Walter, S
Wedemeyer, N
Hasenbank, R
Scherzinger, E
Eickhoff, H
Bates, GP
Lehrach, H
Wanker, EE
机构
[1] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
[2] United Med & Dent Sch Guys & St Thomas Hosp, Guys Hosp, Div Med & Mol Genet, London SE1 7EH, England
关键词
D O I
10.1016/S1097-2765(00)80142-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mechanism by which aggregated polyglns cause the selective neurodegeneration in Huntington's disease (HD) is unknown. Here, we show that the SH3GL3 protein, which is preferentially expressed in brain and testis, selectively interacts with the HD exon 1 protein (HDex1p) containing a glutamine repeat in the pathological range and promotes the formation of insoluble polyglutamine-containing aggregates in vivo. The C-terminal SH3 domain in SH3GL3 and the proline-rich region in HDex1p are essential for the interaction. Coimmunoprecipitations and immunofluorescence studies revealed that SH3GL3 and HDex1p colocalize in transfected COS cells. Additionally, an anti-SH3GL3 antibody was also able to coimmunoprecipitate the full-length huntingtin from an HD human brain extract. The characteristics of the interaction between SH3GL3 and huntingtin and the colocalization of the two proteins suggest that SH3GL3 could be involved in the selective neuronal cell death in HD.
引用
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页码:427 / 436
页数:10
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