ArticleNature communications2020
Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
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- Insulin-induced gene 2 alleviates ischemia-reperfusion injury in steatotic liver by inhibiting GPX4-dependent ferroptosis.Cell death discovery · 2025Article
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- Cysteine sulfenylation contributes to liver fibrosis via the regulation of EphB2-mediated signaling.Cell death & disease · 2024Article
- Arachidonic Acid Mobilization and Peroxidation Promote Microglial Dysfunction in Aβ Pathology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Polyphenols alleviate metabolic disorders: the role of ubiquitin-proteasome system.Frontiers in nutrition · 2024Review
- AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model.Acta neuropathologica · 2023Article
- SEL1L-HRD1 endoplasmic reticulum-associated degradation controls STING-mediated innate immunity by limiting the size of the activable STING pool.Nature cell biology · 2023Article
- Parkin regulates neuronal lipid homeostasis through SREBP2-lipoprotein lipase pathway-implications for Parkinson's disease.Human molecular genetics · 2023Article
- A new dawn beyond lysine ubiquitination.Nature chemical biology · 2022Review
- Non-lysine ubiquitylation: Doing things differently.Frontiers in molecular biosciences · 2022Review
- The GR-gp78 Pathway is involved in Hepatic Lipid Accumulation Induced by Overexpression of 11β-HSD1.International journal of biological sciences · 2022Article
- Cholesterol and Hedgehog Signaling: Mutual Regulation and Beyond.Frontiers in cell and developmental biology · 2022Review
- Review
- Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- SUMOylation of the ubiquitin ligase IDOL decreases LDL receptor levels and is reversed by SENP1.The Journal of biological chemistryArticle
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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