ArticleProceedings of the National Academy of Sciences of the United States of America1998
Apoprotein B100 has a prolonged interaction with the translocon during which its lipidation and translocation change from dependence on the microsomal triglyceride transfer protein to independence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 120 citations in OpenAlex.
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Differential transport pathways of saturated and unsaturated fatty acid esters in male mouse hepatocytes.Nature communications · 2025Article
- Molecular Regulation and Therapeutic Targeting of VLDL Production in Cardiometabolic Disease.Cellular and molecular gastroenterology and hepatology · 2025Review
- Pla2g12b drives expansion of triglyceride-rich lipoproteins.Nature communications · 2024Article
- Hsp40s play distinct roles during the initial stages of apolipoprotein B biogenesis.Molecular biology of the cell · 2022Article
- The Targeting of Native Proteins to the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway: An Expanding Repertoire of Regulated Substrates.Biomolecules · 2021Review
- Protein quality control in the secretory pathway.The Journal of cell biology · 2019Review
- Can modulators of apolipoproteinB biogenesis serve as an alternate target for cholesterol-lowering drugs?Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Review
- Endoplasmic Reticulum-Associated Degradation and Lipid Homeostasis.Annual review of nutrition · 2016Review
- Insights from human congenital disorders of intestinal lipid metabolism.Journal of lipid research · 2015Review
- Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion.Journal of biomedical research · 2014Article
- Cotranslational folding inhibits translocation from within the ribosome-Sec61 translocon complex.Nature structural & molecular biology · 2014Article
- ESCRT regulates surface expression of the Kir2.1 potassium channel.Molecular biology of the cell · 2014Article
- Protein disulfide isomerases contribute differentially to the endoplasmic reticulum-associated degradation of apolipoprotein B and other substrates.Molecular biology of the cell · 2012Article
- Ubiquitination regulates the assembly of VLDL in HepG2 cells and is the committing step of the apoB-100 ERAD pathway.Journal of lipid research · 2011Article
- Huh-7 or HepG2 cells: which is the better model for studying human apolipoprotein-B100 assembly and secretion?Journal of lipid research · 2011Article
- Apolipoprotein B-containing lipoprotein assembly in microsomal triglyceride transfer protein-deficient McA-RH7777 cells.Journal of lipid research · 2010Article
- Impaired-inactivation of FoxO1 contributes to glucose-mediated increases in serum very low-density lipoprotein.Endocrinology · 2010Article
- Arylacetamide deacetylase attenuates fatty-acid-induced triacylglycerol accumulation in rat hepatoma cells.Journal of lipid research · 2010Article
- The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism.Journal of lipid research · 2009Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
When lipid synthesis is limited in HepG2 cells, apoprotein B100 (apoB100) is not secreted but rapidly degraded by the ubiquitin-proteasome pathway. To investigate apoB100 biosynthesis and secretion further, the physical and functional states of apoB100 destined for either degradation or lipoprotein assembly were studied under conditions in which lipid synthesis, proteasomal activity, and microsomal triglyceride transfer protein (MTP) lipid-transfer activity were varied. Cells were pretreated with a proteasomal inhibitor (which remained with the cells throughout the experiment) and radiolabeled for 15 min. During the chase period, labeled apoB100 remained associated with the microsomes. Furthermore, by crosslinking sec61beta to apoB100, we showed that apoB100 remained close to the translocon at the same time apoB100-ubiquitin conjugates could be detected. When lipid synthesis and lipoprotein assembly/secretion were stimulated by adding oleic acid (OA) to the chase medium, apoB100 was deubiquitinated, and its interaction with sec61beta was disrupted, signifying completion of translocation concomitant with the formation of lipoprotein particles. MTP participates in apoB100 translocation and lipoprotein assembly. In the presence of OA, when MTP lipid-transfer activity was inhibited at the end of pulse labeling, apoB100 secretion was abolished. In contrast, when the labeled apoB100 was allowed to accumulate in the cell for 60 min before adding OA and the inhibitor, apoB100 lipidation and secretion were no longer impaired. Overall, the data imply that during most of its association with the endoplasmic reticulum, apoB100 is close to or within the translocon and is accessible to both the ubiquitin-proteasome and lipoprotein-assembly pathways. Furthermore, MTP lipid-transfer activity seems to be necessary only for early translocation and lipidation events.
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