ArticleThe Journal of biological chemistry2012
Fibroblast growth factor-21 (FGF21) regulates low-density lipoprotein receptor (LDLR) levels in cells via the E3-ubiquitin ligase Mylip/Idol and the Canopy2 (Cnpy2)/Mylip-interacting saposin-like protein (Msap).
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 66 citations in OpenAlex.
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- Cell apoptosis in ischemic stroke: Focus on lipid metabolism.Neural regeneration research · 2026Article
- Multifaceted role of CNPY2 beyond ER stress: Disease implications and therapeutic potential.Cell stress · 2026Article
- A novel TLR4 accessory molecule drives hepatic oncogenesis through tumor-associated macrophages.Cancer letters · 2025Article
- Review
- The role of canopy family proteins: biological mechanism and disease function.Molecular biology reports · 2025Review
- CNPY2 protects against ER stress and is expressed by corticostriatal neurons together with CTIP2 in a mouse model of Huntington's disease.Frontiers in molecular neuroscience · 2024Article
- The Effects of Rumen-Protected Choline and Rumen-Protected Nicotinamide on Liver Transcriptomics in Periparturient Dairy Cows.Metabolites · 2023Article
- A machine-learning algorithm integrating baseline serum proteomic signatures predicts exercise responsiveness in overweight males with prediabetes.Cell reports. Medicine · 2023Article
- Effects of Fibroblast Growth Factor 21 on Lactate Uptake and Usage in Mice with Diabetes-Associated Cognitive Decline.Molecular neurobiology · 2022Article
- Article
- CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids.Nature communications · 2022Article
- FGF21 Reduces Lipid Accumulation in Bovine Hepatocytes by Enhancing Lipid Oxidation and Reducing Lipogenesis via AMPK Signaling.Animals : an open access journal from MDPI · 2022Article
- FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases.Frontiers in endocrinology · 2020Review
- Caspase-2 and p75 neurotrophin receptor (p75NTR) are involved in the regulation of SREBP and lipid genes in hepatocyte cells.Cell death & disease · 2019Article
- Characterization of CNPY5 and its family members.Protein science : a publication of the Protein Society · 2019Article
- The roles of FGF21 in atherosclerosis pathogenesis.Reviews in endocrine & metabolic disorders · 2019Review
- Feedback regulation of RTK signaling in development.Developmental biology · 2019Review
- Novel tricyclic glycal-basedMedChemComm · 2018Article
- Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The LDLR is a critical factor in the regulation of blood cholesterol levels that are altered in different human diseases. The level of LDLR in the cell is regulated by both transcriptional and post-transcriptional events. The E3 ubiquitin ligase, myosin regulatory light chain-interacting protein (Mylip)/inducible degrader of the LDL-R (Idol) was shown to induce degradation of LDLR via protein ubiquitination. We have here studied novel factors and mechanisms that may regulate Mylip/Idol in human hepatocyte cells and in mouse macrophages. We observed that FGF21 that is present in serum in different conditions reduced Mylip/Idol at the RNA and protein level, and increased LDLR levels and stability in the cells. FGF21 also enhanced expression of Canopy2 (Cnpy2)/MIR-interacting Saposin-like protein (Msap) that is known to interact with Mylip/Idol. Overexpression of Cnpy2/Msap increased LDLRs, and knockdown experiments showed that Cnpy2/Msap is crucial for the FGF21 effect on LDLRs. Experiments using DiI-labeled LDL particles showed that FGF21 increased lipoprotein uptake and the effect of FGF21 was additive to that of statins. Our results are consistent with an important role of FGF21 and Cnpy2/Msap in the regulation of LDLRs in cultured cells, which warrants further studies using human samples.
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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.