ArticleMolecular biology of the cell2012
Differential regulation of HMG-CoA reductase and Insig-1 by enzymes of the ubiquitin-proteasome system.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
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- Polyphenols alleviate metabolic disorders: the role of ubiquitin-proteasome system.Frontiers in nutrition · 2024Review
- Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Functional significance of cholesterol metabolism in cancer: from threat to treatment.Experimental & molecular medicine · 2023Review
- PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- Chemical chaperones ameliorate neurodegenerative disorders in Derlin-1-deficient mice via improvement of cholesterol biosynthesis.Scientific reports · 2022Article
- Endoplasmic Reticulum-Associated Protein Degradation.Cold Spring Harbor perspectives in biology · 2022Review
- Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome.Chemical research in toxicology · 2022Article
- Altered Cholesterol Homeostasis in Huntington's Disease.Frontiers in aging neuroscience · 2022Review
- A structurally conserved site in AUP1 binds the E2 enzyme UBE2G2 and is essential for ER-associated degradation.PLoS biology · 2021Article
- ERAD components Derlin-1 and Derlin-2 are essential for postnatal brain development and motor function.iScience · 2021Article
- Genetic variation of RNF145 gene and blood lipid levels in Xinjiang population, China.Scientific reports · 2021Article
- The Heat Shock Protein 40-Type Chaperone MASH Supports the Endoplasmic Reticulum-Associated Degradation E3 Ubiquitin Ligase MAKIBISHI1 inFrontiers in plant science · 2021Article
- Post-translational control of the long and winding road to cholesterol.The Journal of biological chemistry · 2020Review
- Article
- Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy.Frontiers in oncology · 2020Review
- ER-associated degradation in health and disease - from substrate to organism.Journal of cell science · 2019Review
- Ubiquitin-dependent protein degradation at the endoplasmic reticulum and nuclear envelope.Seminars in cell & developmental biology · 2019Review
- Schnyder corneal dystrophy-associated UBIAD1 mutations cause corneal cholesterol accumulation by stabilizing HMG-CoA reductase.PLoS genetics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
The endoplasmic reticulum (ER)-resident enzyme 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase catalyzes the rate-limiting step in sterol production and is the therapeutic target of statins. Understanding HMG-CoA reductase regulation has tremendous implications for atherosclerosis. HMG-CoA reductase levels are regulated in response to sterols both transcriptionally, through a complex regulatory loop involving the ER Insig proteins, and posttranslationally, by Insig-dependent protein degradation by the ubiquitin-proteasome system. The ubiquitin ligase (E3) gp78 has been implicated in the sterol-regulated degradation of HMG-CoA reductase and Insig-1 through ER-associated degradation (ERAD). More recently, a second ERAD E3, TRC8, has also been reported to play a role in the sterol-accelerated degradation of HMG-CoA reductase. We interrogated this network in gp78(-/-) mouse embryonic fibroblasts and also assessed two fibroblast cell lines using RNA interference. Although we consistently observe involvement of gp78 in Insig-1 degradation, we find no substantive evidence to support roles for either gp78 or TRC8 in the robust sterol-accelerated degradation of HMG-CoA reductase. We discuss factors that might lead to such discrepant findings. Our results suggest a need for additional studies before definitive mechanistic conclusions are drawn that might set the stage for development of drugs to manipulate gp78 function in metabolic disorders.
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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.