ArticleThe Journal of biological chemistry2011
The sterol-sensing domain (SSD) directly mediates signal-regulated endoplasmic reticulum-associated degradation (ERAD) of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase isozyme Hmg2.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Triazole Stress Induces Accelerated Degradation ofbioRxiv : the preprint server for biology · 2026Article
- The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms.Current issues in molecular biology · 2025Review
- Acquired amphotericin B resistance leads to fitness trade-offs that can be mitigated by compensatory evolution in Candida auris.Nature microbiology · 2024Article
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- Are Point Mutations in HMG-CoA Reductases (Hmg1 and Hmg2) a Step towards Azole Resistance inMolecules (Basel, Switzerland) · 2021Article
- Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy.Frontiers in oncology · 2021Review
- The Heat Shock Protein 40-Type Chaperone MASH Supports the Endoplasmic Reticulum-Associated Degradation E3 Ubiquitin Ligase MAKIBISHI1 inFrontiers in plant science · 2021Article
- Overexpression of Key Sterol Pathway Enzymes in Two Model Marine Diatoms Alters Sterol Profiles inPharmaceuticals (Basel, Switzerland) · 2020Article
- A Cyp51B Mutation Contributes to Azole Resistance inJournal of fungi (Basel, Switzerland) · 2020Article
- Article
- Hydrophobic Cholesteryl Moieties Trigger Substrate Cell-Membrane Interaction of Elastin-Mimetic Protein Coatings in Vitro.ACS omega · 2019Article
- Mutations inmBio · 2019Article
- Therapeutic targets of hypercholesterolemia: HMGCR and LDLR.Diabetes, metabolic syndrome and obesity : targets and therapy · 2019Article
- Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease.International journal of molecular sciences · 2018Review
- Non-cyp51A Azole-Resistant Aspergillus fumigatus Isolates with Mutation in HMG-CoA Reductase.Emerging infectious diseases · 2018Article
- "Mallostery"-ligand-dependent protein misfolding enables physiological regulation by ERAD.The Journal of biological chemistry · 2018Article
- Proteostatic Tactics in the Strategy of Sterol Regulation.Annual review of cell and developmental biology · 2017Review
- Endoplasmic reticulum proteostasis in hepatic steatosis.Nature reviews. Endocrinology · 2016Review
- Identifying novel protein phenotype annotations by hybridizing protein-protein interactions and protein sequence similarities.Molecular genetics and genomics : MGG · 2016Article
- Lipid-regulated degradation of HMG-CoA reductase and Insig-1 through distinct mechanisms in insect cells.Journal of lipid research · 2013Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The sterol-sensing domain (SSD) is a conserved motif in membrane proteins responsible for sterol regulation. Mammalian proteins SREBP cleavage-activating protein (SCAP) and HMG-CoA reductase (HMGR) both possess SSDs required for feedback regulation of sterol-related genes and sterol synthetic rate. Although these two SSD proteins clearly sense sterols, the range of signals detected by this eukaryotic motif is not clear. The yeast HMG-CoA reductase isozyme Hmg2, like its mammalian counterpart, undergoes endoplasmic reticulum (ER)-associated degradation that is subject to feedback control by the sterol pathway. The primary degradation signal for yeast Hmg2 degradation is the 20-carbon isoprene geranylgeranyl pyrophosphate, rather than a sterol. Nevertheless, the Hmg2 protein possesses an SSD, leading us to test its role in feedback control of Hmg2 stability. We mutated highly conserved SSD residues of Hmg2 and evaluated regulated degradation. Our results indicated that the SSD was required for sterol pathway signals to stimulate Hmg2 ER-associated degradation and was employed for detection of both geranylgeranyl pyrophosphate and a secondary oxysterol signal. Our data further indicate that the SSD allows a signal-dependent structural change in Hmg2 that promotes entry into the ER degradation pathway. Thus, the eukaryotic SSD is capable of significant plasticity in signal recognition or response. We propose that the harnessing of cellular quality control pathways to bring about feedback regulation of normal proteins is a unifying theme for the action of all SSDs.
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