ArticleMolecular biology of the cell2013
Ancient ubiquitous protein-1 mediates sterol-induced ubiquitination of 3-hydroxy-3-methylglutaryl CoA reductase in lipid droplet-associated endoplasmic reticulum membranes.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 79 citations in OpenAlex.
- The Hrd1-Mediated ERAD Pathway in Plants: Conserved Principles and Plant-Specific Innovations.International journal of molecular sciences · 2026Review
- AUP1 and UBE2G2 complex targets STING signaling and regulates virus-induced innate immunity.mBio · 2025Article
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- A nanobody that binds to the backside of the ubiquitin conjugating enzyme Ube2G2 differentially affects interactions with its partner E3 Ligases.Communications biology · 2025Article
- An integrated analysis of multiple datasets reveals novel gene signatures in human granulosa cells.Scientific data · 2024Article
- Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.Biomolecules · 2024Article
- Integrating single-cell analysis and machine learning to create glycosylation-based gene signature for prognostic prediction of uveal melanoma.Frontiers in endocrinology · 2023Article
- Lipid Droplets and Their Participation in Zika Virus Infection.International journal of molecular sciences · 2022Review
- AUP1 regulates lipid metabolism and induces lipid accumulation to accelerate the progression of renal clear cell carcinoma.Cancer science · 2022Article
- Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.Molecular neurobiology · 2022Review
- HDL and Lipid Metabolism.Advances in experimental medicine and biology · 2022Article
- A structurally conserved site in AUP1 binds the E2 enzyme UBE2G2 and is essential for ER-associated degradation.PLoS biology · 2021Article
- Protein Quality Control and Lipid Droplet Metabolism.Annual review of cell and developmental biology · 2020Review
- Unraveling the regulatory role of endoplasmic-reticulum-associated degradation in tumor immunity.Critical reviews in biochemistry and molecular biology · 2020Review
- A Review of Diatom Lipid Droplets.Biology · 2020Review
- Article
- Lipid Droplet Contacts With Autophagosomes, Lysosomes, and Other Degradative Vesicles.Contact (Thousand Oaks (Ventura County, Calif.)) · 2020Article
- Comparative proteomic study of liver lipid droplets and mitochondria in mice housed at different temperatures.FEBS letters · 2019Article
- Dynamics and functions of lipid droplets.Nature reviews. Molecular cell biology · 2019Review
- Assays for protein retrotranslocation in ERAD.Methods in enzymology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Sterol-induced binding to Insigs in endoplasmic reticulum (ER) membranes triggers ubiquitination of the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase. This ubiquitination, which is mediated by Insig-associated ubiquitin ligases gp78 and Trc8, is obligatory for extraction of reductase from lipid droplet-associated ER membranes into the cytosol for proteasome-mediated, ER-associated degradation (ERAD). In this study, we identify lipid droplet-associated, ancient, ubiquitous protein-1 (Aup1) as one of several proteins that copurify with gp78. RNA interference (RNAi) studies show that Aup1 recruits the ubiquitin-conjugating enzyme Ubc7 to lipid droplets and facilitates its binding to both gp78 and Trc8. The functional significance of these interactions is revealed by the observation that RNAi-mediated knockdown of Aup1 blunts sterol-accelerated ubiquitination of reductase, which appears to occur in lipid droplet-associated membranes and subsequent ERAD of the enzyme. In addition, Aup1 knockdown inhibits ERAD of Insig-1, another substrate for gp78, as well as that of membrane-bound precursor forms of sterol-regulatory, element-binding protein-1 and -2, transcription factors that modulate expression of genes encoding enzymes required for cholesterol synthesis. Considered together, these findings not only implicate a role for Aup1 in maintenance of intracellular cholesterol homeostasis, but they also highlight the close connections among ERAD, lipid droplets, and lipid droplet-associated proteins.
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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.