ArticleThe EMBO journal2007
The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2.
Article in The EMBO journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers.
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Who cites it
168 citing papers in PubMed, 276 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer.Cell death & disease · 2026Article
- Gemella morbillorum Promotes Colorectal Carcinogenesis: LPBDCP-Mediated Invasion Activates Ras Signaling and Destabilizes p53.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- USP21 functions as an oncogenic regulator of the Mdm2-p53 axis in colorectal cancer.Cell death discovery · 2026Article
- Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains.Nature communications · 2026Article
- Ubiquitin-Specific Protease 2 (USP2) as a Modulator of Energy Metabolism: A Review of Studies Using Animal and Cellular Models.Biomedicines · 2026Review
- CD47 destabilization via manipulating the SPOP-USP2 axis augments macrophage phagocytosis and cancer immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Exploring the prognostic molecular mechanisms of medulloblastoma through methylation-transcriptome integration.SAGE open medicine · 2026Article
- Targeting USP2 induces degradation of PML-RARα with or without drug-resistant mutations in acute promyelocytic leukemia.Acta biochimica et biophysica Sinica · 2025Article
- USP38 functions as an oncoprotein by downregulating the p53 pathway through deubiquitination and stabilization of MDM2.Cell death and differentiation · 2025Article
- USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity.Nature communications · 2025Article
- Key roles of ubiquitination in regulating critical regulators of cancer stem cell functionality.Genes & diseases · 2025Review
- Oncogenic and immunological functions of USP35 in pan-cancer and its potential as a biomarker in kidney clear cell carcinoma.BMC cancer · 2025Article
- Roles of deubiquitinases in urologic cancers (Review).Oncology letters · 2024Review
- ATXN3: a multifunctional protein involved in the polyglutamine disease spinocerebellar ataxia type 3.Expert reviews in molecular medicine · 2024Review
- Roles of naïve CD4Journal of translational medicine · 2024Article
- USP19 Negatively Regulates p53 and Promotes Cervical Cancer Progression.Molecular biotechnology · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- The deubiquitinating enzyme USP44 suppresses hepatocellular carcinoma progression by inhibiting Hedgehog signaling and PDL1 expression.Cell death & disease · 2023Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
108 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mdm2 is an E3 ubiquitin ligase that promotes its own ubiquitination and also ubiquitination of the p53 tumour suppressor. In a bacterial two-hybrid screen, using Mdm2 as bait, we identified an Mdm2-interacting peptide that bears sequence similarity to the deubiquitinating enzyme USP2a. We have established that full-length USP2a associates with Mdm2 in cells where it can deubiquitinate Mdm2 while demonstrating no deubiquitinating activity towards p53. Ectopic expression of USP2a causes accumulation of Mdm2 in a dose-dependent manner and consequently promotes Mdm2-mediated p53 degradation. This differs from the behaviour of HAUSP, which deubiquitinates p53 in addition to Mdm2 and thus protects p53 from Mdm2-mediated degradation. We further demonstrate that suppression of endogenous USP2a destabilises Mdm2 and causes accumulation of p53 protein and activation of p53. Our data identify the deubiquitinating enzyme USP2a as a novel regulator of the p53 pathway that acts through its ability to selectively target Mdm2.
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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.