ArticleThe Journal of biological chemistry2009
Insulin enhances post-translational processing of nascent SREBP-1c by promoting its phosphorylation and association with COPII vesicles.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 131 citations in OpenAlex.
- A novel JNK2/SREBP-1c pathway involved in insulin-induced fatty acid synthesis in human adipocytes.Journal of lipid research · 2013Trial
- Article
- Renalase deficiency suppresses hepatic triglyceride accumulation in the progression to MASLD/MASH by GAN diet in male mice.Physiological reports · 2026Article
- Mechanisms of COPII coat assembly and cargo recognition in the secretory pathway.Nature reviews. Molecular cell biology · 2025Review
- Article
- Unlocking the lipid code: SREBPs as key drivers in gastrointestinal tumour metabolism.Lipids in health and disease · 2025Review
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- Activation of the mTOR pathway enhances PPARγ/SREBP-mediated lipid synthesis in human meibomian gland epithelial cells.Scientific reports · 2024Article
- α-Tocopherol reduces VLDL secretion through modulation of intracellular ER-to-Golgi transport of VLDL.Canadian journal of physiology and pharmacology · 2023Article
- Endothelial cell-derived stem cell factor promotes lipid accumulation through c-Kit-mediated increase of lipogenic enzymes in brown adipocytes.Nature communications · 2023Article
- DIAPH1 mediates progression of atherosclerosis and regulates hepatic lipid metabolism in mice.Communications biology · 2023Article
- Long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.Nature communications · 2023Article
- PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A.Oncology research · 2023Article
- Important Hormones Regulating Lipid Metabolism.Molecules (Basel, Switzerland) · 2022Review
- An IGF-1R-mTORC1-SRPK2 signaling Axis contributes to FASN regulation in breast cancer.BMC cancer · 2022Article
- Visualization and quantification ofAnnals of translational medicine · 2022Article
- Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD.Seminars in liver disease · 2022Review
- An AKT/PRMT5/SREBP1 axis in lung adenocarcinoma regulates de novo lipogenesis and tumor growth.Cancer science · 2021Article
- Hepatic transcriptional responses to fasting and feeding.Genes & development · 2021Review
- Dairy Foods and Dairy Fats: New Perspectives on Pathways Implicated in Cardiometabolic Health.Advances in nutrition (Bethesda, Md.) · 2020Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The regulation of lipid homeostasis by insulin is mediated in part by the enhanced transcription of the gene encoding SREBP-1c (sterol regulatory element-binding protein-1c). Nascent SREBP-1c is synthesized and embedded in the endoplasmic reticulum (ER) and must be transported to the Golgi in coatomer protein II (COPII) vesicles where two sequential cleavages generate the transcriptionally active NH(2)-terminal fragment, nSREBP-1c. There is limited indirect evidence to suggest that insulin may also regulate the posttranslational processing of the nascent SREBP-1c protein. Therefore, we designed experiments to directly assess the action of insulin on the post-translational processing of epitope-tagged full-length SREBP-1c and SREBP-2 proteins expressed in cultured hepatocytes. We demonstrate that insulin treatment led to enhanced post-translational processing of SREBP-1c, which was associated with phosphorylation of ER-bound nascent SREBP-1c protein that increased affinity of the SREBP-1c cleavage-activating protein (SCAP)-SREBP-1c complex for the Sec23/24 proteins of the COPII vesicles. Furthermore, chemical and molecular inhibitors of the phosphoinositide 3-kinase pathway and its downstream kinase protein kinase B (PKB)/Akt prevented both insulin-mediated phosphorylation of nascent SREBP-1c protein and its posttranslational processing. Insulin had no effect on the proteolysis of nascent SREBP-2 under identical conditions. We also show that in vitro incubation of an active PKB/Akt enzyme with recombinant full-length SREBP-1c led to its phosphorylation. Thus, insulin selectively stimulates the processing of SREBP-1c in rat hepatocytes by enhancing the association between the SCAP-SREBP-1c complex and COPII proteins and subsequent ER to Golgi transport and proteolytic cleavage. This effect of insulin is tightly linked to phosphoinositide 3-kinase and PKB/Akt-dependent serine phosphorylation of the precursor SREBP-1c protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.