ArticleOncogenesis2017
The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2 and differentially affect its function.
Article in Oncogenesis, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- The deubiquitinase USP4 stabilizes the SCFNature communications · 2026Article
- Review
- Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential.Molecular oncology · 2024Review
- HAS2 facilitates glioma cell malignancy and suppresses ferroptosis in an FZD7-dependent manner.Cancer science · 2024Article
- The Role of Ubiquitination in Osteosarcoma Development and Therapies.Biomolecules · 2024Review
- Deubiquitylating Enzymes in Cancer and Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy.Experimental hematology & oncology · 2023Review
- Identification of a Small Molecule Inhibitor of Hyaluronan Synthesis, DDIT, Targeting Breast Cancer Cells.Cancers · 2022Article
- Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review).International journal of oncology · 2022Review
- USP14 Regulates Cancer Cell Growth in a Fatty Acid Synthase-Independent Manner.International journal of molecular sciences · 2021Article
- The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review.Cancer cell international · 2021Review
- Article
- Spotlight on USP4: Structure, Function, and Regulation.Frontiers in cell and developmental biology · 2021Review
- The Effects of the Transforming Growth Factor-β1 (TGF-β1) Signaling Pathway on Cell Proliferation and Cell Migration are Mediated by Ubiquitin Specific Protease 4 (USP4) in Hypertrophic Scar Tissue and Primary Fibroblast Cultures.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- USP4 function and multifaceted roles in cancer: a possible and potential therapeutic target.Cancer cell international · 2020Review
- Deubiquitinating Enzymes: A Critical Regulator of Mitosis.International journal of molecular sciences · 2019Review
- Article
- USP4 positively regulates RLR-induced NF-κB activation by targeting TRAF6 for K48-linked deubiquitination and inhibits enterovirus 71 replication.Scientific reports · 2018Article
- Tricho-rhino-phalangeal syndrome 1 protein functions as a scaffold required for ubiquitin-specific protease 4-directed histone deacetylase 2 de-ubiquitination and tumor growth.Breast cancer research : BCR · 2018Article
- Clinicopathological Significance of DUB3 Expression in Non-small Cell Lung Cancer and Relationship Between DUB3 Expression and LATS1 Expression.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The levels of hyaluronan, a ubiquitous glycosaminoglycan prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20). Hyaluronan accumulates in rapidly remodeling tissues, such as breast cancer, due to deregulated expression of the HAS2 gene and/or alterations of HAS2 activity. The activity of HAS2 is regulated by post-translational modifications, including ubiquitination. In order to identify deubiquitinating enzymes (DUBs) that are involved in de-ubiquitination of HAS2, a complementary (cDNA) library of 69 Flag-HA-tagged human DUBs cloned into retroviral vectors was screened in human embryonic kidney (HEK) 293T cells for their ability to de-ubiquitinate myc-tagged HAS2. Several DUBs were found to decrease the ubiquitination of 6myc-HAS2, among which, the most effective were USP17 and USP4. USP17 efficiently removed polyubiquitination, whereas USP4 preferentially removed monoubiquitination of 6myc-HAS2. Co-immunoprecipitation studies revealed interactions between HAS2 and USP17, as well as between HAS2 and USP4, in membrane preparations of HEK293T cells. USP17 significantly stabilized 6myc-HAS2 protein levels, whereas USP4 did not. The silencing of USP17 led to decreased hyaluronan production, whereas the suppression of USP4 increased hyaluronan synthesis. Importantly, high levels of USP17 and HAS2 were detected in a panel of cancer cell lines compared to normal cells, and immunohistochemical stainings revealed higher expression of USP17 and HAS2 in tissues of lung cancer patients compared to normal tissue. In conclusion, USP17 and USP4 differently affect HAS2 ubiquitination, and the stability and function of HAS2.
Identifiers
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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.