期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：20
页码：11723-11728
DOI：10.1073/pnas.1934748100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Intracellular deposition of aggregated and ubiquitinated proteins is a prominent cytopathological feature of most neurodegenerative disorders frequently correlated with neural cell death. To elucidate mechanisms in neural cell death and degeneration, we characterized the Drosophila ortholog of Sec61 (DSec61), a component of the translocon that is involved in both protein import and endoplasmic reticulum-associated degradation. Loss-of-function experiments for DSec61 revealed that the translocon contributes to expanded polyglutamine-mediated neuronal toxicity, likely resulting from proteasome inhibition and leading to accumulation of ubiquitinated proteins. Taken together, proteasome inhibition by expanded polyglutamine tracts may lead to the accumulation of toxic undegraded proteins normally transported by the Sec61 translocon.
