ArticleeLife2015
The prenyltransferase UBIAD1 is the target of geranylgeraniol in degradation of HMG CoA reductase.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 85 citations in OpenAlex.
- Farnesol and geranylgeraniol in plant reproduction: insights from Arabidopsis and beyond.Journal of experimental botany · 2026Review
- Prenols and prenoic acids in metabolism, disease, and aging.Journal of lipid research · 2026Review
- Uncovering protein prenylation in Th1 cells: novel prenylation sites and insights into statin and farnesyltransferase inhibition.BMC biology · 2025Article
- Host-Derived Geranylgeraniol Shields Intraerythrocytic Stages of Malaria Parasites from Fosmidomycin.Research square · 2025Article
- 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
- Article
- Disrupting cholesterol homeostasis in T cells boosts antitumour responses.Nature metabolism · 2025Article
- Hepatic lipid metabolism is altered in Ubiad1Scientific reports · 2025Article
- Properties and medical applications of the Euphorbiaceae family and their bioproducts: a patent review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- A pipeline for identification of causal mutations in barley identifies Xantha-j as the chlorophyll synthase gene.Plant physiology · 2024Article
- Revisiting the interconnection between lipids and vitamin K metabolism: insights from recent research and potential therapeutic implications: a review.Nutrition & metabolism · 2024Review
- Decoding the crosstalk between mevalonate metabolism and T cell function.Immunological reviews · 2023Review
- Vitamin K and the Visual System-A Narrative Review.Nutrients · 2023Review
- Potential role of geranylgeraniol in managing statin-associated muscle symptoms: a COVID-19 related perspective.Frontiers in physiology · 2023Article
- Androgen-Independent Prostate Cancer Is Sensitive to CDC42-PAK7 Kinase Inhibition.Biomedicines · 2022Article
- Post-Translational Regulation of HMG CoA Reductase.Cold Spring Harbor perspectives in biology · 2022Review
- Regulated degradation of HMG CoA reductase requires conformational changes in sterol-sensing domain.Nature communications · 2022Article
- Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation.The FEBS journal · 2022Article
- UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult.Cell & bioscience · 2022Article
- Order through destruction: how ER-associated protein degradation contributes to organelle homeostasis.The EMBO journal · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Schnyder corneal dystrophy (SCD) is an autosomal dominant disorder in humans characterized by abnormal accumulation of cholesterol in the cornea. SCD-associated mutations have been identified in the gene encoding UBIAD1, a prenyltransferase that synthesizes vitamin K2. Here, we show that sterols stimulate binding of UBIAD1 to the cholesterol biosynthetic enzyme HMG CoA reductase, which is subject to sterol-accelerated, endoplasmic reticulum (ER)-associated degradation augmented by the nonsterol isoprenoid geranylgeraniol through an unknown mechanism. Geranylgeraniol inhibits binding of UBIAD1 to reductase, allowing its degradation and promoting transport of UBIAD1 from the ER to the Golgi. CRISPR-CAS9-mediated knockout of UBIAD1 relieves the geranylgeraniol requirement for reductase degradation. SCD-associated mutations in UBIAD1 block its displacement from reductase in the presence of geranylgeraniol, thereby preventing degradation of reductase. The current results identify UBIAD1 as the elusive target of geranylgeraniol in reductase degradation, the inhibition of which may contribute to accumulation of cholesterol in SCD.
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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.