ArticleNature communications2023
Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 34 citations in OpenAlex.
- PRKX-mediated stabilization of PD-L1 characterizes an immunosuppressive gastric cancer subtype.Journal for immunotherapy of cancer · 2026Article
- USP2 is an androgen-repressed survival factor that stabilises oncoproteins to facilitate therapy resistance in prostate cancer.Cell death & disease · 2026Article
- Endothelial USP2a-METTL16 loop potentiates IL-6 signaling via mCell death and differentiation · 2026Article
- CD47 destabilization via manipulating the SPOP-USP2 axis augments macrophage phagocytosis and cancer immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Suppression of USP2 in mouse skeletal muscle: a model of oxidative stress in muscle tissue.Experimental animals · 2026Article
- The deubiquitinase USP35: from an oncogenic hub to a therapeutic target in human cancers.Frontiers in oncology · 2026Review
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- USP2-mediated PPARγ stabilization promotes hepatocellular carcinoma progression and M2 macrophage polarization via oleic acid.Journal for immunotherapy of cancer · 2025Article
- Deubiquitinase-dependent transcriptional silencing controls inflammation.Cell research · 2025Article
- DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis.Cell death & disease · 2025Article
- Biochemical analysis of PD-L1 ubiquitination by CRL3Structure (London, England : 1993) · 2025Article
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Protease regulation of tumor-immune cell symbiosis.Trends in cancer · 2025Review
- USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity.Nature communications · 2025Article
- USP2-induced upregulation of LEF1 through deubiquitination relieves osteoporosis development by promoting the osteogenic differentiation of bone marrow mesenchymal stem cells.Journal of orthopaedic surgery and research · 2025Article
- Oncogenic and immunological functions of USP35 in pan-cancer and its potential as a biomarker in kidney clear cell carcinoma.BMC cancer · 2025Article
- Lactylation-driven transcriptional activation of FBXO33 promotes gallbladder cancer metastasis by regulating p53 polyubiquitination.Cell death & disease · 2025Article
- Unveiling the nexus of p53 and PD-L1: insights into immunotherapy resistance mechanisms in hepatocellular carcinoma.American journal of cancer research · 2025Review
- Targeting ferroptosis: a promising avenue for ovarian cancer treatment.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Since Mdm2 (Mouse double minute 2) inhibitors show serious toxicity in clinic studies, different approaches to achieve therapeutic reactivation of p53-mediated tumor suppression in cancers need to be explored. Here, we identify the USP2 (ubiquitin specific peptidase 2)-VPRBP (viral protein R binding protein) axis as an important pathway for p53 regulation. Like Mdm2, VPRBP is a potent repressor of p53 but VPRBP stability is controlled by USP2. Interestingly, the USP2-VPRBP axis also regulates PD-L1 (programmed death-ligand 1) expression. Strikingly, the combination of a small-molecule USP2 inhibitor and anti-PD1 monoclonal antibody leads to complete regression of the tumors expressing wild-type p53. In contrast to Mdm2, knockout of Usp2 in mice has no obvious effect in normal tissues. Moreover, no obvious toxicity is observed upon the USP2 inhibitor treatment in vivo as Mdm2-mediated regulation of p53 remains intact. Our study reveals a promising strategy for p53-based therapy by circumventing the toxicity issue.
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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.