ArticleProceedings of the National Academy of Sciences of the United States of America2018
Control of CCND1 ubiquitylation by the catalytic SAGA subunit USP22 is essential for cell cycle progression through G1 in cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 122 citations in OpenAlex.
- Mapping and visualization of global research progress on deubiquitinases in ovarian cancer: a bibliometric analysis.Frontiers in pharmacology · 2024Pooled it
- Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.Signal transduction and targeted therapy · 2022Trial
- SIRT2-mediated deacetylation activates USP22 catalytic function for PD-L1 protein stabilization and tumor immune escape.The Journal of clinical investigation · 2026Article
- Decoding the Oncogenic Role of USP22 Through Pan-Cancer Genomic and Epigenetic Analysis.Cancer reports (Hoboken, N.J.) · 2026Article
- Targeting ubiquitin-specific peptidase 22 in solid tumours: from ubiquitination to immunotherapy.Frontiers in cell and developmental biology · 2026Review
- The WWP1-JARID1B axis sustains acute myeloid leukemia chemoresistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- USP22 enhances atherosclerotic plaque stability and macrophage efferocytosis by stabilizing PPARγ.Communications biology · 2025Article
- Tissue-Specific Expression of the PorcineAnimals : an open access journal from MDPI · 2025Article
- GABRD Accelerates Tumour Progression via Regulating CCND1 Signalling Pathway in Gastric Cancer.Journal of cellular and molecular medicine · 2025Article
- Inhibition of Retinal Neovascularization by BEZ235: Targeting the Akt/4EBP1/Cyclin D1 Pathway in Endothelial Cells.Investigative ophthalmology & visual science · 2025Article
- Bioinformatic analysis of the role of USP22 expression in hepatocellular carcinoma.International journal of clinical and experimental pathology · 2025Article
- USP22 Promotes Osteosarcoma Progression by Stabilising β-Catenin and Upregulating HK2 and Glycolysis.Journal of cellular and molecular medicine · 2024Article
- Review
- Hepatocyte growth factor promotes melanoma metastasis through ubiquitin-specific peptidase 22-mediated integrins upregulation.Cancer letters · 2024Article
- Ubiquitin-Specific Protease 22 Plays a Key Role in Increasing Extracellular Vesicle Secretion and Regulating Cell Motility of Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ubiquitin-specific peptidase 22 controls integrin-dependent cancer cell stemness and metastasis.iScience · 2024Article
- Natural variation in GmSW17 controls seed size in soybean.Nature communications · 2024Article
- Epinephrine promotes breast cancer metastasis through a ubiquitin-specific peptidase 22-mediated lipolysis circuit.Science advances · 2024Article
- The secoiridoid glycoside Gentiopicroside is a USP22 inhibitor with potent antitumor immunotherapeutic activity.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a marker of aggressive cancer phenotypes like metastasis, therapy resistance, and poor survival. Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others. Current models suggest that USP22 mediates these biological effects via its role in epigenetic regulation as a subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor complex. Challenging the dogma, we report here a nontranscriptional role for USP22 via a direct effect on the core cell cycle machinery: that is, the deubiquitylation of the G1 cyclin D1 (CCND1). Deubiquitylation by USP22 protects CCND1 from proteasome-mediated degradation and occurs separately from the canonical phosphorylation/ubiquitylation mechanism previously shown to regulate CCND1 stability. We demonstrate that control of CCND1 is a key mechanism by which USP22 mediates its known role in cell cycle progression. Finally, USP22 and CCND1 levels correlate in patient lung and colorectal cancer samples and our preclinical studies indicate that targeting USP22 in combination with CDK inhibitors may offer an approach for treating cancer patients whose tumors exhibit elevated CCND1.
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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.