文章基本信息

标题：Mahogunin ring finger-1 (MGRN1) Suppresses Chaperone-Associated Misfolded Protein Aggregation and Toxicity
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作者：Deepak Chhangani ; Amit Mishra
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2013
卷号：3
DOI：10.1038/srep01972
出版社：Springer Nature
摘要：Impairment in the elimination of misfolded proteins generates cellular toxicity and leads to various late-onset neurodegenerative diseases. However, the mechanisms by which cells recognize abnormal cellular proteins for selective clearance remain unknown. Lack of the mahogunin ring finger-1 (MGRN1) E3 ubiquitin ligase in mice causes the development of age-dependent spongiform neurodegeneration. Here, we report for the first time that the MGRN1 E3 ubiquitin ligase interacts and nicely co-localizes with the cytosolic molecular chaperone Hsp70. The expression of MGRN1 increased following exposure to a variety of stressors. The inhibition of autophagy not only elevated endogenous MGRN1 levels but also caused MGRN1 to be recruited to cytosolic ubiquitin-positive inclusion bodies. Finally, we showed that the overexpression of MGRN1 protects against cell death mediated by oxidative and endoplasmic reticulum stress. These data suggest that MGRN1 selectively targets misfolded proteins for degradation and may exhibit viable therapeutic potential for the treatment of spongiform neurodegeneration.