ArticleThe Journal of cell biology1992
Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for enzyme degradation in the endoplasmic reticulum.
Article in The Journal of cell biology, 1992. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 185 citations in OpenAlex.
- Allosteric regulation of UBIAD1 trafficking from ER to Golgi revealed by chemical genetic screening.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Lipid liquid-crystalline nanoparticles as a suitable platform for accommodating sensitive membrane proteins: monitoring the activity of HMG-CoA reductase.Journal of nanobiotechnology · 2025Article
- Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.Biomolecules · 2024Article
- Direct binding to sterols accelerates endoplasmic reticulum-associated degradation of HMG CoA reductase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Statin Action Targets Lipid Rafts of Cell Membranes: GIXD/PM-IRRAS Investigation of Langmuir Monolayers.The journal of physical chemistry. B · 2023Article
- Post-Translational Regulation of HMG CoA Reductase.Cold Spring Harbor perspectives in biology · 2022Review
- Model Lipid Raft Membranes for Embedding Integral Membrane Proteins: Reconstitution of HMG-CoA Reductase and Its Inhibition by Statins.Langmuir : the ACS journal of surfaces and colloids · 2022Article
- Metabolic features of innate lymphoid cells.The Journal of experimental medicine · 2022Review
- Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain.Nature communications · 2022Article
- Synthesis, function, and regulation of sterol and nonsterol isoprenoids.Frontiers in molecular biosciences · 2022Review
- Lactobacillus mediates the expression of NPC1L1, CYP7A1, and ABCG5 genes to regulate cholesterol.Food science & nutrition · 2021Review
- Article
- Monomeric NADH-Oxidizing Methylenetetrahydrofolate Reductases from Mycobacterium smegmatis Lack Flavin Coenzyme.Journal of bacteriology · 2020Article
- Schnyder corneal dystrophy-associated UBIAD1 is defective in MK-4 synthesis and resists autophagy-mediated degradation.Journal of lipid research · 2020Article
- Construction ofFrontiers in cell and developmental biology · 2020Article
- Porcine HMGCR Inhibits Porcine Circovirus Type 2 Infection by Directly Interacting with the Viral Proteins.Viruses · 2019Article
- Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Discovery of a potent HMG-CoA reductase degrader that eliminates statin-induced reductase accumulation and lowers cholesterol.Nature communications · 2018Article
- Underlying mechanisms for sterol-induced ubiquitination and ER-associated degradation of HMG CoA reductase.Seminars in cell & developmental biology · 2018Review
- Potential Pathogenic Role of Anti-Signal Recognition Protein and Anti-3-hydroxy-3-methylglutaryl-CoA Reductase Antibodies in Immune-Mediated Necrotizing Myopathies.Current rheumatology reports · 2018Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We have raised two monospecific antibodies against synthetic peptides derived from the membrane domain of the ER glycoprotein 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate limiting enzyme in the cholesterol biosynthetic pathway. This domain, which was proposed to span the ER membrane seven times (Liscum, L., J. Finer-Moore, R. M. Stroud, K. L. Luskey, M. S. Brown, and J. L. Goldstein. 1985. J. Biol. Chem. 260:522-538), plays a critical role in the regulated degradation of the enzyme in the ER in response to sterols. The antibodies stain the ER of cells and immunoprecipitate HMG-CoA reductase and HMGal, a chimeric protein composed of the membrane domain of the reductase fused to Escherichia coli beta-galactosidase, the degradation of which is also accelerated by sterols. We show that the sequence Arg224 through Leu242 of HMG-CoA reductase (peptide G) faces the cytoplasm both in cultured cells and in rat liver, whereas the sequence Thr284 through Glu302 (peptide H) faces the lumen of the ER. This indicates that a sequence between peptide G and peptide H spans the membrane of the ER. Moreover, by epitope tagging with peptide H, we show that the loop segment connecting membrane spans 3 and 4 is sequestered in the lumen of the ER. These results demonstrate that the membrane domain of HMG-CoA reductase spans the ER eight times and are inconsistent with the seven membrane spans topological model. The approximate boundaries of the proposed additional transmembrane segment are between Lys248 and Asp276. Replacement of this 7th span in HMGal with the first transmembrane helix of bacteriorhodopsin abolishes the sterol-enhanced degradation of the protein, indicating its role in the regulated turnover of HMG-CoA reductase within the endoplasmic reticulum.
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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.