ArticleTraffic (Copenhagen, Denmark)2015
Endocytosis of Ubiquitylation-Deficient EGFR Mutants via Clathrin-Coated Pits is Mediated by Ubiquitylation.
Article in Traffic (Copenhagen, Denmark), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Small-molecule CBLB inhibitor abolishes EGFR ubiquitination, reduces receptor endocytosis, and diminishes cell motility signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Small-molecule CBLB inhibitor abolishes EGFR ubiquitination, reduces receptor endocytosis and diminishes cell motility signaling.bioRxiv : the preprint server for biology · 2026Article
- Poly-ubiquitylated transmembrane proteins outcompete other cargo for limited space inside clathrin-coated vesicles.Cell reports · 2025Article
- Laminar organization of molecular complexes in a clathrin coat revealed by nanoscale protein colocalization.Structure (London, England : 1993) · 2025Article
- Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes.Molecular biology of the cell · 2023Article
- Hypoxic stress disrupts HGF/Met signaling in human trophoblasts: implications for the pathogenesis of preeclampsia.Journal of biomedical science · 2022Article
- Article
- Mechanism of p38 MAPK-induced EGFR endocytosis and its crosstalk with ligand-induced pathways.The Journal of cell biology · 2021Article
- Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis.Annual review of biochemistry · 2021Review
- Knockout of c-Cbl slows EGFR endocytic trafficking and enhances EGFR signaling despite incompletely blocking receptor ubiquitylation.Pharmacology research & perspectives · 2021Article
- Ubiquitin chains earmark GPCRs for BBSome-mediated removal from cilia.The Journal of cell biology · 2020Article
- An internally eGFP-tagged α-adaptin is a fully functional and improved fiduciary marker for clathrin-coated pit dynamics.Traffic (Copenhagen, Denmark) · 2020Article
- Evolution of an Amniote-Specific Mechanism for Modulating Ubiquitin Signaling via Phosphoregulation of the E2 Enzyme UBE2D3.Molecular biology and evolution · 2020Article
- Molecularly Distinct Clathrin-Coated Pits Differentially Impact EGFR Fate and Signaling.Cell reports · 2019Article
- Article
- Cbl interacts with multiple E2s in vitro and in cells.PloS one · 2019Article
- cIAP1 regulates the EGFR/Snai2 axis in triple-negative breast cancer cells.Cell death and differentiation · 2018Article
- A conformational sensor based on genetic code expansion reveals an autocatalytic component in EGFR activation.Nature communications · 2018Article
- Genome-edited human stem cells expressing fluorescently labeled endocytic markers allow quantitative analysis of clathrin-mediated endocytosis during differentiation.The Journal of cell biology · 2018Article
- Unique auto-ubiquitination activities of artificial RING fingers in cancer cells.Protein science : a publication of the Protein Society · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Signaling by epidermal growth factor receptor (EGFR) is controlled by endocytosis. However, mechanisms of EGFR endocytosis remain poorly understood. Here, we found that the EGFR mutant lacking known ubiquitylation, acetylation and clathrin adaptor AP-2-binding sites (21KRΔAP2) was internalized at relatively high rates via the clathrin-dependent pathway in human duodenal adenocarcinoma HuTu-80 cells. RNA interference analysis revealed that this residual internalization is strongly inhibited by depletion of Grb2 and the E2 ubiquitin-conjugating enzyme UbcH5b/c, and partially affected by depletion of the E3 ubiquitin ligase Cbl and ubiquitin-binding adaptors, indicating that an ubiquitylation process is involved. Several new ubiquitin conjugation sites were identified by mass spectrometry in the 21KRΔAP2 mutant, suggesting that cryptic ubiquitylation may mediate endocytosis of this mutant. Total internal reflection fluorescence microscopy imaging of HuTu-80 cells transfected with labeled ubiquitin adaptor epsin1 demonstrated that the ubiquitylation-deficient EGFR mutant was endocytosed through a limited population of epsin-enriched clathrin-coated pits (CCPs), although with a prolonged CCP lifetime. Native EGFR was recruited with the same efficiency into CCPs containing either AP-2 or epsin1 that were tagged with fluorescent proteins by genome editing of MDA-MD-231 cells. We propose that two redundant mechanisms, ubiquitylation and interaction with AP-2, contribute to EGFR endocytosis via CCPs in a stochastic fashion.
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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.