ArticleThe EMBO journal2019
Endosome and Golgi-associated degradation (EGAD) of membrane proteins regulates sphingolipid metabolism.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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70 citing papers in PubMed, 113 citations in OpenAlex.
- Mechanisms of Quality Control in GPI-Anchored Proteins: The Central Role of the Lipid Anchor.International journal of molecular sciences · 2026Review
- Plasma proteome differences between giant cell arteritis and polymyalgia rheumatica: a pilot study.Arthritis research & therapy · 2026Article
- Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion.Cellular & molecular biology letters · 2026Review
- ORMDL Proteins Turnover via Proteasome and Autophagy Is Cell-Type Dependent and Tied to Ceramide Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Cystinosin/Ers1 functions in redox homeostasis in the early secretory pathway.bioRxiv : the preprint server for biology · 2026Article
- Investigating and correcting a rare pathogenic mutation in GDF11.HGG advances · 2026Article
- K48-ubiquitin-dependent proteases cut-up post-ER proteins.Nature communications · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence.The EMBO journal · 2025Article
- Sphingolipid and methionine metabolism in aging.Journal of cell science · 2025Review
- Orm2 promotes nitrogen-induced sphingolipid production and endocytosis via Orm1 phosphorylation.Journal of lipid research · 2025Article
- Intricate Regulation of Sphingolipid Biosynthesis: An In-Depth Look Into ORMDL-Mediated Regulation of Serine Palmitoyltransferase.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Ubiquitin chain variability directs substrates of the Tul1 ubiquitin ligase complex to different degradation pathways.The Journal of cell biology · 2025Article
- Tom40 functions as a channel for protein retrotranslocation in the mitochondria-associated degradation (MAD) pathway.Communications biology · 2025Article
- Lysosomal quality control Review.Autophagy · 2025Review
- D-mannose suppresses the angiogenesis and progression of colorectal cancer.Acta biochimica et biophysica Sinica · 2025Article
- Different Proteostasis Mechanisms Facilitate the Assembly of Individual Components on the Chitin Synthase 3 Complex at the Endoplasmic Reticulum.Journal of fungi (Basel, Switzerland) · 2025Article
- Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression.Molecular oncology · 2025Article
- Non-autophagic Golgi-LC3 lipidation facilitates TFE3 stress response against Golgi dysfunction.The EMBO journal · 2024Article
- The Dsc complex and its role in Golgi quality control.Biochemical Society transactions · 2024Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Cellular homeostasis requires the ubiquitin-dependent degradation of membrane proteins. This was assumed to be mediated exclusively either by endoplasmic reticulum-associated degradation (ERAD) or by endosomal sorting complexes required for transport (ESCRT)-dependent lysosomal degradation. We identified in Saccharomyces cerevisiae an additional pathway that selectively extracts membrane proteins at Golgi and endosomes for degradation by cytosolic proteasomes. One endogenous substrate of this endosome and Golgi-associated degradation pathway (EGAD) is the ER-resident membrane protein Orm2, a negative regulator of sphingolipid biosynthesis. Orm2 degradation is initiated by phosphorylation, which triggers its ER export. Once on Golgi and endosomes, Orm2 is poly-ubiquitinated by the membrane-embedded "Defective in SREBP cleavage" (Dsc) ubiquitin ligase complex. Cdc48/VCP then extracts ubiquitinated Orm2 from membranes, which is tightly coupled to the proteasomal degradation of Orm2. Thereby, EGAD prevents the accumulation of Orm2 at the ER and in post-ER compartments and promotes the controlled de-repression of sphingolipid biosynthesis. Thus, the selective degradation of membrane proteins by EGAD contributes to proteostasis and lipid homeostasis in eukaryotic cells.
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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.