TorsinA protein degradation and autophagy in DYT1 dystonia.
TorsinA protein degradation and autophagy in DYT1 dystonia.
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DOI：
10.4161/auto.5.1.7173
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发表时间：
2009-01
期刊：
影响因子：
13.3
通讯作者：
Chin, Lih-Shen
中科院分区：
文献类型：
--
作者：
Giles, Lisa M.;Li, Lian;Chin, Lih-Shen
关键词：
Early-onset generalized dystonia (DYT1) is a debilitating neurological disorder characterized by involuntary movements and sustained muscle spasms. DYT1 dystonia has been associated with two mutations in torsinA that result in the deletion of a single glutamate residue (torsinA ΔE) and six amino-acid residues (torsinA Δ323-8). We recently revealed that torsinA, a peripheral membrane protein, which resides predominantly in the lumen of the endoplasmic reticulum (ER) and nuclear envelope (NE), is a long-lived protein whose turnover is mediated by basal autophagy. Dystonia-associated torsinA ΔE and torsinA Δ323-8 mutant proteins show enhanced retention in the NE and accelerated degradation by both the proteasome and autophagy. Our results raise the possibility that the monomeric form of torsinA mutant proteins is cleared by proteasome-mediated ER-associated degradation (ERAD), whereas the oligomeric and aggregated forms of torsinA mutant proteins are cleared by ER stress-induced autophagy. Our findings provide new insights into the pathogenic mechanism of torsinA ΔE and torsinA Δ323-8 mutations in dystonia and emphasize the need for a mechanistic understanding of the role of autophagy in protein quality control in the ER and NE compartments.
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DOI：
10.1073/pnas.0304375101
发表时间：
2004-01-20
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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