دورية أكاديمية
أعرض في EDS

Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2.

التفاصيل البيبلوغرافية
العنوان: Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2.
المؤلفون: Zhou ZS; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Li MX; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Liu J; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Jiao H; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Xia JM; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Shi XJ; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Zhao H; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Chu L; School of Life Science and Technology, ShanghaiTech Universiy, Shanghai, 201203, China., Liu J; School of Life Science and Technology, ShanghaiTech Universiy, Shanghai, 201203, China., Qi W; School of Life Science and Technology, ShanghaiTech Universiy, Shanghai, 201203, China., Luo J; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China., Song BL; Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, China. blsong@whu.edu.cn.
المصدر: Nature communications [Nat Commun] 2020 Jan 17; Vol. 11 (1), pp. 379. Date of Electronic Publication: 2020 Jan 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Ubiquitination*, Cysteine/*metabolism , Membrane Proteins/*metabolism , Receptors, Autocrine Motility Factor/*metabolism, Amphibians ; Animals ; CHO Cells ; Cell Line ; Cricetulus ; Down-Regulation ; Evolution, Molecular ; Fishes ; Hepatocytes/metabolism ; Humans ; Lipid Metabolism ; Lipogenesis ; Liver/metabolism ; Male ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle Cells/metabolism ; Muscle Fibers, Skeletal/metabolism ; Myoblasts/metabolism ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Receptors, Autocrine Motility Factor/genetics ; Sequence Analysis, Protein ; Sterol Regulatory Element Binding Proteins/metabolism ; Transcriptome
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.
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المشرفين على المادة: 0 (Insig2 protein, mouse)
0 (Membrane Proteins)
0 (Reactive Oxygen Species)
0 (Sterol Regulatory Element Binding Proteins)
EC 2.3.2.27 (Amfr protein, mouse)
EC 2.3.2.27 (Receptors, Autocrine Motility Factor)
K848JZ4886 (Cysteine)
تواريخ الأحداث: Date Created: 20200119 Date Completed: 20200409 Latest Revision: 20240725
رمز التحديث: 20240726
مُعرف محوري في PubMed: PMC6969111
DOI: 10.1038/s41467-019-14231-w
PMID: 31953408
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-019-14231-w