دورية أكاديمية
Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2
| العنوان: | Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2 |
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| المؤلفون: | Zhou, Zhang-Sen, Li, Mei-Xin, Liu, Jie, Jiao, Hengwu, Xia, Jing-Ming, Shi, Xiong-Jie, Zhao, Huabin, Chu, Liping, Liu, Jingrong, Qi, Wei, Luo, Jie, Song, Bao-Liang |
| المساهمون: | National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Ministry of Education of China | Chinese Service Center for Scholarly Exchange |
| المصدر: | Nature Communications ; volume 11, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | Insig-2 is an ER membrane protein negatively controlling lipid biosynthesis. Here, we find that Insig-2 is increased in the tissues, including liver, but unaltered in the muscle of gp78 -deficient mice. In hepatocytes and undifferentiated C2C12 myoblasts, Insig-2 is ubiquitylated on Cys215 by gp78 and degraded. However, the C215 residue is oxidized by elevated reactive oxygen species (ROS) during C2C12 myoblasts differentiating into myotubes, preventing Insig-2 from ubiquitylation and degradation. The stabilized Insig-2 downregulates lipogenesis through inhibiting the SREBP pathway, helping to channel the carbon flux to ATP generation and protecting myotubes from lipid over-accumulation. Evolutionary analysis shows that the YECK (in which C represents Cys215 in human Insig-2) tetrapeptide sequence in Insig-2 is highly conserved in amniotes but not in aquatic amphibians and fishes, suggesting it may have been shaped by differential selection. Together, this study suggests that competitive oxidation-ubiquitylation on Cys215 of Insig-2 senses ROS and prevents muscle cells from lipid accumulation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-019-14231-w |
| الإتاحة: | https://doi.org/10.1038/s41467-019-14231-wTest https://www.nature.com/articles/s41467-019-14231-w.pdfTest https://www.nature.com/articles/s41467-019-14231-wTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.4C7C5864 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-14231-w |
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