ArticleJournal of lipid research2011
Ubiquitination regulates the assembly of VLDL in HepG2 cells and is the committing step of the apoB-100 ERAD pathway.
Article in Journal of lipid research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- A suite of genome-engineered hepatic cells provides novel insights into the spatiotemporal metabolism of apolipoprotein B and apolipoprotein B-containing lipoprotein secretion.Cardiovascular research · 2024Article
- VLDL Biogenesis and Secretion: It Takes a Village.Circulation research · 2024Review
- Ultrasensitive and High-Resolution Protein Spatially Decoding Framework for Tumor Extracellular Vesicles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Developmental Differences between Anthers of Diploid and Autotetraploid Rice at Meiosis.Plants (Basel, Switzerland) · 2022Article
- Hsp40s play distinct roles during the initial stages of apolipoprotein B biogenesis.Molecular biology of the cell · 2022Article
- Overlapping function of Hrd1 and Ste24 in translocon quality control provides robust channel surveillance.The Journal of biological chemistry · 2020Article
- Endoplasmic reticulum stress-regulated degradation of a translocon-associated protein is independent of integrated stress response transcription factor Gcn4p.microPublication biology · 2020Article
- Glucose concentration does not affect degradation of a protein that aberrantly engages the endoplasmic reticulum translocon.microPublication biology · 2020Article
- Cathepsin B regulates hepatic lipid metabolism by cleaving liver fatty acid-binding protein.The Journal of biological chemistry · 2018Article
- Membrane Protein Quantity Control at the Endoplasmic Reticulum.The Journal of membrane biology · 2017Review
- Article
- Endoplasmic Reticulum-Associated Degradation and Lipid Homeostasis.Annual review of nutrition · 2016Review
- Upregulated expression of ubiquitin-conjugating enzyme E2Q1 (UBE2Q1) is associated with enhanced cell proliferation and poor prognosis in human hapatocellular carcinoma.Journal of molecular histology · 2015Article
- Ubiquitin ligases in cholesterol metabolism.Diabetes & metabolism journal · 2014Review
- Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion.Journal of biomedical research · 2014Article
- ESCRT regulates surface expression of the Kir2.1 potassium channel.Molecular biology of the cell · 2014Article
- Aberrant substrate engagement of the ER translocon triggers degradation by the Hrd1 ubiquitin ligase.The Journal of cell biology · 2012Article
- Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk.Journal of lipid research · 2011Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apolipoprotein B-100 (apoB-100) is degraded by endoplasmic reticulum-associated degradation (ERAD) when lipid availability limits assembly of VLDLs. The ubiquitin ligase gp78 and the AAA-ATPase p97 have been implicated in the proteasomal degradation of apoB-100. To study the relationship between ERAD and VLDL assembly, we used small interfering RNA (siRNA) to reduce gp78 expression in HepG2 cells. Reduction of gp78 decreased apoB-100 ubiquitination and cytosolic apoB-ubiquitin conjugates. Radiolabeling studies revealed that gp78 knockdown increased secretion of newly synthesized apoB-100 and, unexpectedly, enhanced VLDL assembly, as the shift in apoB-100 density in gp78-reduced cells was accompanied by increased triacylglycerol (TG) secretion. To explore the mechanisms by which gp78 reduction might enhance VLDL assembly, we compared the effects of gp78 knockdown with those of U0126, a mitogen-activated protein kinase/ERK kinase1/2 inhibitor that enhances apoB-100 secretion in HepG2 cells. U0126 treatment increased secretion of both apoB100 and TG and decreased the ubiquitination and cellular accumu-lation of apoB-100. Furthermore, p97 knockdown caused apoB-100 to accumulate in the cell, but if gp78 was concomitantly reduced or assembly was enhanced by U0126 treatment, cellular apoB-100 returned toward baseline. This indicates that ubiquitination commits apoB-100 to p97-mediated retrotranslocation during ERAD. Thus, decreasing ubiquitination of apoB-100 enhances VLDL assembly, whereas improving apoB-100 lipidation decreases its ubiquitination, suggesting that ubiquitination has a regulatory role in VLDL assembly.
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