ArticleNature cell biology2017
Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation.
Article in Nature cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 136 citations in OpenAlex.
- Machine Learning Predicts Treatment Response and Prognostic Pathways From Whole-Blood Transcriptome in Primary Biliary Cholangitis.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Article
- The mechanism of dynamic equilibrium of ascorbate redox status mediated by PbrDHAR5 during scald development in pear fruit.Molecular horticulture · 2026Article
- E3 ligase AREL1 controls perinuclear localization of lysosomes and supports Purkinje cell survival.The EMBO journal · 2026Article
- A novel SO2 probe inhibits lysophagy induced by Senecavirus A infection by promoting LAMP1 Cys375 sulfenylation.PLoS pathogens · 2026Article
- Research Advances in Nanodrugs Targeting Lipid Metabolism Reprogramming for Colorectal Cancer Therapy.International journal of nanomedicine · 2026Review
- ELOVL6 Promotes the Proliferation and Migration of Oral Squamous Cell Carcinoma Cells Through Fatty Acid Remodelling and ROS Modulation in vitro.OncoTargets and therapy · 2026Article
- Remodelled cholesteryl ester enriched lipid droplets fuel flavivirus morphogenesis.bioRxiv : the preprint server for biology · 2025Article
- Impact Induces Phagocytic Defect in Reactive Microglia.bioRxiv : the preprint server for biology · 2025Article
- Remodeling adipocytes' lipid metabolism with a polycation loaded enzyme-active framework reverses osteoporotic bone marrow.Nature communications · 2025Article
- Integrative analysis of metabolomics and transcriptomics reveals alterations in egg quality and hepatic lipid metabolism in hens supplemented with curcumin.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- Chronic Exposure to Environmental Concentrations of Tetrabromobisphenol A Disrupts Insulin and Lipid Homeostasis in Diet-Induced Obese Mice.Environmental science & technology · 2025Article
- Radiotherapy as salvage therapy and an adjunct to immunotherapy: exploring local and abscopal mechanisms to overcome immunotherapy resistance: a narrative review.Translational lung cancer research · 2025Review
- Exploring the role of curcumin in mitigating oxidative stress to alleviate lipid metabolism disorders.Frontiers in pharmacology · 2025Review
- Vitamin A family suppresses periodontitis by restoring mitochondrial metabolic reprogramming in macrophages through JAK-STAT pathway.Frontiers in genetics · 2025Article
- Ubiquitination in lipid metabolism reprogramming: implications for pediatric solid tumors.Frontiers in immunology · 2025Review
- Epigenetics disruptions enabled by porphyrin-derived metal-organic frameworks disarm resistances to sonocatalytic ROS anti-tumor actions.Fundamental research · 2025Article
- Microbial-transcriptome integrative analysis of heat stress effects on amino acid metabolism and lipid peroxidation in poultry jejunum.Animal biotechnology · 2024Article
- Up-regulation of MSMO1 was associated with poor survival in cervical cancer.Translational cancer research · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Ubiquitin linkage to cysteine is an unconventional modification targeting protein for degradation. However, the physiological regulation of cysteine ubiquitylation is still mysterious. Here we found that ACAT2, a cellular enzyme converting cholesterol and fatty acid to cholesteryl esters, was ubiquitylated on Cys277 for degradation when the lipid level was low. gp78-Insigs catalysed Lys48-linked polyubiquitylation on this Cys277. A high concentration of cholesterol and fatty acid, however, induced cellular reactive oxygen species (ROS) that oxidized Cys277, resulting in ACAT2 stabilization and subsequently elevated cholesteryl esters. Furthermore, ACAT2 knockout mice were more susceptible to high-fat diet-associated insulin resistance. By contrast, expression of a constitutively stable form of ACAT2 (C277A) resulted in higher insulin sensitivity. Together, these data indicate that lipid-induced stabilization of ACAT2 ameliorates lipotoxicity from excessive cholesterol and fatty acid. This unconventional cysteine ubiquitylation of ACAT2 constitutes an important mechanism for sensing lipid-overload-induced ROS and fine-tuning lipid homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
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.