ArticleMolecular biology of the cell2005
Regulation of epidermal growth factor receptor down-regulation by UBPY-mediated deubiquitination at endosomes.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 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
143 citing papers in PubMed, 281 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- Elucidation of short linear motif-based interactions of the MIT and rhodanese domains of the ubiquitin-specific protease 8.Biology direct · 2025Article
- Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinoma.NPJ precision oncology · 2025Article
- Deubiquitinases and Cancer.Journal of pharmacy & bioallied sciences · 2024Review
- Cushing's Disease Manifestation inInternational journal of molecular sciences · 2024Article
- Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturation.eLife · 2024Article
- Erasing marks: Functions of plant deubiquitylating enzymes in modulating the ubiquitin code.The Plant cell · 2024Review
- USP8 prevents aberrant NF-κB and Nrf2 activation by counteracting ubiquitin signals from endosomes.The Journal of cell biology · 2024Article
- A heterozygous germline deletion within USP8 causes severe neurodevelopmental delay with multiorgan abnormalities.Journal of human genetics · 2024Article
- Extracellular targeted protein degradation: an emerging modality for drug discovery.Nature reviews. Drug discovery · 2024Review
- Review
- Review
- Proteomic approaches to study ubiquitinomics.Biochimica et biophysica acta. Gene regulatory mechanisms · 2023Review
- Targeted therapy for cisplatin-resistant lung cancer via aptamer-guided nano-zinc carriers containing USP14 siRNA.MedComm · 2023Article
- Impact of epidermal growth factor and/or β-mercaptoethanol supplementations on theFrontiers in veterinary science · 2023Article
- Transcriptomic Profiles of Normal Pituitary Cells and Pituitary Neuroendocrine Tumor Cells.Cancers · 2022Review
- Article
- Targeting Deubiquitinating Enzymes (DUBs) That Regulate Mitophagy via Direct or Indirect Interaction with Parkin.International journal of molecular sciences · 2022Review
- P720R USP8 Mutation Is Associated with a Better Responsiveness to Pasireotide in ACTH-Secreting PitNETs.Cancers · 2022Article
- The Induced Expression ofInternational journal of molecular sciences · 2022Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ligand-activated receptor tyrosine kinases undergo endocytosis and are transported via endosomes to lysosomes for degradation. This "receptor down-regulation" process is crucial to terminate the cell proliferation signals produced by activated receptors. During the process, ubiquitination of the receptors serves as a sorting signal for their trafficking from endosomes to lysosomes. Here, we describe the role of a deubiquitinating enzyme UBPY/USP8 in the down-regulation of epidermal growth factor (EGF) receptor (EGFR). Overexpression of UBPY reduced the ubiquitination level of EGFR and delayed its degradation in EGF-stimulated cells. Immunopurified UBPY deubiquitinated EGFR in vitro. In EGF-stimulated cells, UBPY underwent ubiquitination and bound to EGFR. Overexpression of Hrs or a dominant-negative mutant of SKD1, proteins that play roles in the endosomal sorting of ubiquitinated receptors, caused the accumulation of endogenous UBPY on exaggerated endosomes. A catalytically inactive UBPY mutant clearly localized on endosomes, where it overlapped with EGFR when cells were stimulated with EGF. Finally, depletion of endogenous UBPY by RNA interference resulted in elevated ubiquitination and accelerated degradation of EGF-activated EGFR. We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes.
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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.