ArticleThe Journal of biological chemistry2020
Ring finger protein 5 activates sterol regulatory element-binding protein 2 (SREBP2) to promote cholesterol biosynthesis via inducing polyubiquitination of SREBP chaperone SCAP.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- PDE5A Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking through a Noncanonical cGMP-Dependent Pathway.Cancer research · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- ICOS regulates IL-10 production in group 2 innate lymphoid cells via cholesterol and cortisol biosynthesis.The Journal of clinical investigation · 2025Article
- The role of ubiquitination and deubiquitination in cancer lipid metabolism.Frontiers in oncology · 2025Review
- Vitamin D Is Associated with Lipid Metabolism: A Sex- and Age-Dependent Analysis of a Large Outpatient Cohort.Nutrients · 2024Article
- Ubiquitination and De-Ubiquitination in the Synthesis of Cow Milk Fat: Reality and Prospects.Molecules (Basel, Switzerland) · 2024Review
- LIMA1 links the E3 ubiquitin ligase RNF40 to lipid metabolism.Cell death discovery · 2024Article
- Gallic Acid Can Promote Low-Density Lipoprotein Uptake in HepG2 Cells via Increasing Low-Density Lipoprotein Receptor Accumulation.Molecules (Basel, Switzerland) · 2024Article
- Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.Nature communications · 2023Article
- Parkin regulates neuronal lipid homeostasis through SREBP2-lipoprotein lipase pathway-implications for Parkinson's disease.Human molecular genetics · 2023Article
- Dynamic quality control machinery that operates across compartmental borders mediates the degradation of mammalian nuclear membrane proteins.Cell reports · 2022Article
- MicroRNA-874 targets phosphomevalonate kinase and inhibits cancer cell growth via the mevalonate pathway.Scientific reports · 2022Article
- Pseudorabies virus tegument protein UL13 recruits RNF5 to inhibit STING-mediated antiviral immunity.PLoS pathogens · 2022Article
- Deletion of RNF186 expression suppresses diet-induced hepatic steatosis by regulating insulin activity.iScience · 2022Article
- Intracellular Cholesterol Synthesis and Transport.Frontiers in cell and developmental biology · 2022Review
- PKM2-TMEM33 axis regulates lipid homeostasis in cancer cells by controlling SCAP stability.The EMBO journal · 2021Article
- Prostate Cancer-Focus on Cholesterol.Cancers · 2021Review
- Sterol-resistant SCAP Overexpression in Vascular Smooth Muscle Cells Accelerates Atherosclerosis by Increasing Local Vascular Inflammation through Activation of the NLRP3 Inflammasome in Mice.Aging and disease · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sterol regulatory element-binding protein 2 (SREBP2) is the master transcription factor that regulates cholesterol metabolism. SREBP2 activation is regulated by SREBP chaperone SCAP. Here we show that ring finger protein 5 (RNF5), an endoplasmic reticulum-anchored E3 ubiquitin ligase, mediates the Lys-29-linked polyubiquitination of SCAP and thereby activates SREBP2. RNF5 knockdown inhibited SREBP2 activation and reduced cholesterol biosynthesis in human hepatoma cells, and RNF5 overexpression activated SREBP2. Mechanistic studies revealed that RNF5 binds to the transmembrane domain of SCAP and ubiquitinates the Lys-305 located in cytosolic loop 2 of SCAP. Moreover, the RNF5-mediated ubiquitination enhanced an interaction between SCAP luminal loop 1 and loop 7, a crucial event for SREBP2 activation. Notably, an overexpressed K305R SCAP variant failed to restore the SREBP2 pathway in SCAP-deficient cell lines. These findings define a new mechanism by which an ubiquitination-induced SCAP conformational change regulates cholesterol biosynthesis.
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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.