التفاصيل البيبلوغرافية
| العنوان: |
Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2. |
| 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 |
| المصدر: |
Nature Communications; 1/17/2020, Vol. 11 Issue 1, p1-13, 13p |
| مصطلحات موضوعية: |
UBIQUITINATION, LIVER cells, CYSTEINE, OXIDATION, MEMBRANE proteins, MYOBLASTS, MUSCLE cells |
| مستخلص: |
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. The protein Insig-2 negatively regulates lipid biosynthesis and is short-lived in liver cells but stable in muscle cells. Here, the authors show that in muscle cells producing reactive oxygen species, there is increased oxidation compared to ubiquitination of Insig-2, stabilising Insig-2 and reducing lipid biosynthesis. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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