ArticleOncogene2013
The ubiquitin-specific protease USP2a prevents endocytosis-mediated EGFR degradation.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 70 citations in OpenAlex.
- Rewiring KRAS-driven cancers through the ubiquitin-proteasome system: therapeutic opportunities with a focus on deubiquitinase.Experimental & molecular medicine · 2026Review
- USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer.Cell death & disease · 2026Article
- Downregulation of B7-H4 contributes to the synergistic effect of USP2a-targeted/anti-PD-1 combination therapy in EGFR mutant lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- USP21-EGFR signaling axis is functionally implicated in metastatic colorectal cancer.Cell death discovery · 2024Article
- The impact of nitric oxide on HER family post-translational modification and downstream signaling in cancer.Frontiers in physiology · 2024Review
- Lipid-mediated activation of plasma membrane-localized deubiquitylating enzymes modulate endosomal trafficking.Nature communications · 2022Article
- Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression.Autophagy · 2022Article
- FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.Nature communications · 2021Article
- Ubiquitin-specific protease 2a promotes hepatocellular carcinoma progression via deubiquitination and stabilization of RAB1A.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes.International journal of molecular sciences · 2021Review
- The Cross-Talk Between EGFR and E-Cadherin.Frontiers in cell and developmental biology · 2021Review
- The Inhibitory Effects of 6-Thioguanine and 6-Mercaptopurine on the USP2a Target Fatty Acid Synthase in Human Submaxillary Carcinoma Cells.Frontiers in oncology · 2021Article
- Dysregulation and activities of ubiquitin specific peptidase 2b in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2021Article
- USP25 Regulates EGFR Fate by Modulating EGF-Induced Ubiquitylation Dynamics.Biomolecules · 2020Article
- The deubiquitylase USP2 maintains ErbB2 abundance via counteracting endocytic degradation and represents a therapeutic target in ErbB2-positive breast cancer.Cell death and differentiation · 2020Article
- Advances in Deubiquitinating Enzyme Inhibition and Applications in Cancer Therapeutics.Cancers · 2020Review
- Downregulation of ubiquitin-specific protease 2 possesses prognostic and diagnostic value and promotes the clear cell renal cell carcinoma progression.Annals of translational medicine · 2020Article
- Overexpression of Ubiquitin-Specific Protease 2 (USP2) in the Heart Suppressed Pressure Overload-Induced Cardiac Remodeling.Mediators of inflammation · 2020Article
- The ubiquitin system: orchestrating cellular signals in non-small-cell lung cancer.Cellular & molecular biology letters · 2020Review
- Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene expression and activate lung epithelial cells.Journal of molecular cell biology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Ubiquitination of epidermal growth factor receptor (EGFR) is required for downregulation of the receptor by endocytosis. Impairment of this pathway results in constitutively active EGFR, which is associated with carcinogenesis, particularly in lung cancer. We previously demonstrated that the deubiquitinating enzyme ubiquitin-specific protease 2a (USP2a) has oncogenic properties. Here, we show a new role for USP2a as a regulator of EGFR endocytosis. USP2a localizes to early endosomes and associates with EGFR, stabilizing the receptor, which retains active downstream signaling. HeLa cells transiently expressing catalytically active, but not mutant (MUT), USP2a show increased plasma membrane-localized EGFR, as well as decreased internalized and ubiquitinated EGFR. Conversely, USP2a silencing reverses this phenotype. Importantly, USP2a prevents the degradation of MUT in addition to wild-type EGFR. Finally, we observed that USP2a and EGFR proteins are coordinately overexpressed in non-small cell lung cancers. Taken together, our data indicate that USP2a antagonizes EGFR endocytosis and thus amplifies signaling activity from the receptor. Our findings suggest that regulation of deubiquitination could be exploited therapeutically in cancers overexpressing EGFR.
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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.