ArticleeLife2018
The sterol-responsive RNF145 E3 ubiquitin ligase mediates the degradation of HMG-CoA reductase together with gp78 and Hrd1.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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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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Who cites it
69 citing papers in PubMed, 117 citations in OpenAlex.
- Triazole Stress Induces Accelerated Degradation ofbioRxiv : the preprint server for biology · 2026Article
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Cysteine availability tunes ubiquitin signaling via inverse stability of LRRC58 E3 ligase and its substrate CDO1.Nature communications · 2026Article
- A conserved E3 ubiquitin ligase rewires carotenoid, sterol, and lipid metabolism inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Degrons: defining the rules of protein degradation.Nature reviews. Molecular cell biology · 2025Review
- UBE2J2 sensitizes the ERAD ubiquitination cascade to changes in membrane lipid saturation.Nature communications · 2025Article
- CRISPR-Cas9 genetic screens reveal regulation of TMPRSS2 by the Elongin BC-VHL complex.Scientific reports · 2025Article
- Systematic interrogation of functional genes underlying cholesterol and lipid homeostasis.Genome biology · 2025Article
- A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.The EMBO journal · 2025Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- CompoundAnimal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Roles of posttranslational modifications in lipid metabolism and cancer progression.Biomarker research · 2024Review
- Damaging mutations in liver X receptor-α are hepatotoxic and implicate cholesterol sensing in liver health.Nature metabolism · 2024Article
- Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.The EMBO journal · 2024Article
- Article
- Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models.Molecular cancer therapeutics · 2024Article
- Small-molecule correctors divert CFTR-F508del from ERAD by stabilizing sequential folding states.Molecular biology of the cell · 2024Article
- Review
- Doa10/MARCH6 architecture interconnects E3 ligase activity with lipid-binding transmembrane channel to regulate SQLE.Nature communications · 2024Article
9 more citing papers are in PubMed but not listed here.
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.
Funding
Abstract
Mammalian HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the cholesterol biosynthetic pathway and the therapeutic target of statins, is post-transcriptionally regulated by sterol-accelerated degradation. Under cholesterol-replete conditions, HMGCR is ubiquitinated and degraded, but the identity of the E3 ubiquitin ligase(s) responsible for mammalian HMGCR turnover remains controversial. Using systematic, unbiased CRISPR/Cas9 genome-wide screens with a sterol-sensitive endogenous HMGCR reporter, we comprehensively map the E3 ligase landscape required for sterol-accelerated HMGCR degradation. We find that RNF145 and gp78 independently co-ordinate HMGCR ubiquitination and degradation. RNF145, a sterol-responsive ER-resident E3 ligase, is unstable but accumulates following sterol depletion. Sterol addition triggers RNF145 recruitment to HMGCR via Insigs, promoting HMGCR ubiquitination and proteasome-mediated degradation. In the absence of both RNF145 and gp78, Hrd1, a third UBE2G2-dependent E3 ligase, partially regulates HMGCR activity. Our findings reveal a critical role for the sterol-responsive RNF145 in HMGCR regulation and elucidate the complexity of sterol-accelerated HMGCR degradation. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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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.