ArticleJournal of lipid research2013
Both K63 and K48 ubiquitin linkages signal lysosomal degradation of the LDL receptor.
Article in Journal of lipid research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- Ubiquitin-Specific Protease 20 Promotes CCCP-Induced Mitophagy Through Deubiquitination and Stabilization of Serine/Threonine Protein Kinase PINK1.Journal of molecular neuroscience : MN · 2025Article
- Role of TRIM24 in the regulation of proteasome-autophagy crosstalk in bortezomib-resistant mantle cell lymphoma.Cell death discovery · 2025Article
- TFEB promotes Ginkgetin-induced ferroptosis via TRIM25 mediated GPX4 lysosomal degradation in EGFR wide-type lung adenocarcinoma.Theranostics · 2025Article
- Protein quality control systems in neurodegeneration - culprits, mitigators, and solutions?Frontiers in neurology · 2025Review
- β-Elemene induced ferroptosis via TFEB-mediated GPX4 degradation in EGFR wide-type non-small cell lung cancer.Journal of advanced research · 2024Article
- Lysosome-dependent FOXA1 ubiquitination contributes to luminal lineage of advanced prostate cancer.Molecular oncology · 2023Article
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- KIAA0317 regulates SOCS1 stability to ameliorate colonic inflammation.The FEBS journal · 2023Article
- Regulation of PD-L1 Trafficking from Synthesis to Degradation.Cancer immunology research · 2023Article
- Cul3-KLHL20 E3 ubiquitin ligase plays a key role in the arms race between HIV-1 Nef and host SERINC5 restriction.Nature communications · 2022Article
- Alpha Enolase 1 Ubiquitination and Degradation Mediated byPathogens (Basel, Switzerland) · 2021Article
- The aminosterol Claramine inhibits β-secretase 1-mediated insulin receptor cleavage.The Journal of biological chemistry · 2021Article
- E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy.Clinical and experimental immunology · 2021Review
- Ubiquitin signaling in cell cycle control and tumorigenesis.Cell death and differentiation · 2021Review
- Interferon Receptor Trafficking and Signaling: Journey to the Cross Roads.Frontiers in immunology · 2020Review
- IDOL regulates systemic energy balance through control of neuronal VLDLR expression.Nature metabolism · 2019Article
- LncRNAs-directed PTEN enzymatic switch governs epithelial-mesenchymal transition.Cell research · 2019Article
- Inhibition of low-density lipoprotein receptor degradation with a cyclic peptide that disrupts the homodimerization of IDOL E3 ubiquitin ligase.Chemical science · 2018Article
- DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine.The Journal of clinical investigation · 2018Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Linkage-specific ubiquitination often leads to distinct cellular events. It has been difficult to establish definitively the requirement for a particular linkage in mammalian degradation pathways due to the inability to deplete endogenous ubiquitin while maintaining cell viability. The E3 ubiquitin ligase inducible degrader of the LDL receptor (IDOL) targets the low density lipoprotein receptor (LDLR) for degradation. The nature of the linkages employed to signal lysosomal degradation of the LDLR, and to signal proteasomal autodegradation of IDOL, have not been determined. We used an inducible RNAi strategy to replace endogenous ubiquitin with mutants lacking K48 or K63. We found that IDOL catalyzes the transfer of ubiquitin chains to itself and to the LDLR that do not contain exclusively K48 or K63 linkages. Thus, LDLR can be targeted to the lysosome by either K48 or K63 linkages. We further demonstrate that although both ubiquitin conjugating enzyme E2 (UBE2)Ds and UBE2N/V1 can catalyze LDLR ubiquitination in a cell-free system, UBE2Ds appear to be the major E2 enzymes employed by IDOL in cells, consistent with their ability to catalyze both K48 and K63 linkages. The results reveal mechanistic insight into the posttranscriptional control of lipoprotein uptake and provide a test of the requirement of linkage-specific ubiquitination for specific lysosomal and proteasomal degradation pathways in mammalian cells.
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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.