Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation
| العنوان: | Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation |
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| المؤلفون: | Xiaodong Zhu, Erkang Fei, Huadong Fan, Hongfeng Wang, Jiawei Zhou, Guanghui Wang, Zheng Ying |
| المصدر: | Human Molecular Genetics. 18:4268-4281 |
| بيانات النشر: | Oxford University Press (OUP), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | medicine.medical_specialty, Ubiquitin-Protein Ligases, SOD1, Mutant, Mice, Transgenic, Nerve Tissue Proteins, Biology, Endoplasmic-reticulum-associated protein degradation, Endoplasmic Reticulum, Cell Line, Mice, Superoxide Dismutase-1, Ubiquitin, Internal medicine, Genetics, medicine, Animals, Humans, Receptors, Cytokine, Ataxin-3, Molecular Biology, Genetics (clinical), Superoxide Dismutase, Endoplasmic reticulum, Ubiquitination, Nuclear Proteins, nutritional and metabolic diseases, Neurodegenerative Diseases, General Medicine, nervous system diseases, Ubiquitin ligase, Cell biology, Receptors, Autocrine Motility Factor, Repressor Proteins, Endocrinology, Proteasome, Ataxin, biology.protein, Protein Binding, Transcription Factors |
| الوصف: | Superoxide dismutase-1 (SOD1) and ataxin-3 are two neurodegenerative disease proteins in association with familial amyotrophic lateral sclerosis and Machado-Joseph disease/spinocerebellar ataxia type 3. Both normal and mutant types of SOD1 and ataxin-3 are degraded by the proteasome. It was recently reported that these two proteins are associated with the endoplasmic reticulum (ER). Mammalian gp78 is an E3 ubiquitin ligase involved in ER-associated degradation (ERAD). Here, we show that gp78 interacts with both SOD1 and ataxin-3. Overexpression of gp78 promotes the ubiquitination and degradation of these two proteins, whereas knockdown of gp78 stabilizes them. Moreover, gp78 represses aggregate formation of mutant SOD1 and protect cells against mutant SOD1-induced cell death. Furthermore, gp78 is increased in cells transfected with these two mutant proteins as well as in ALS mice. Thus, our results suggest that gp78 functions in the regulation of SOD1 and ataxin-3 to target them for ERAD. |
| تدمد: | 1460-2083 0964-6906 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::819ec4f3d4456380ada8d54b3f47d6adTest https://doi.org/10.1093/hmg/ddp380Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....819ec4f3d4456380ada8d54b3f47d6ad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602083 09646906 |
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