ArticleThe EMBO journal2022
USP33 deubiquitinates and stabilizes HIF-2alpha to promote hypoxia response in glioma stem cells.
Article in The EMBO journal, 2022. 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, 45 citations in OpenAlex.
- HIFs: The central drivers of tumors and their role as molecular switches in targeted therapy?Acta pharmaceutica Sinica. B · 2026Review
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Current Studies on the Hypoxic Tumor Microenvironment in Thyroid Cancer: From Molecular Mechanisms to Clinical Therapeutic Perspectives.Biomedicines · 2026Review
- Leucine-rich repeats and immunoglobulin-like domains 3 suppresses hypoxia-induced vasculogenic mimicry in glioma by promoting the ubiquitination and degradation of Snail2.Cell stress & chaperones · 2026Article
- Integrated single-cell and spatial transcriptomic profiling decodes lineage plasticity and immune microenvironment remodeling in prostate cancer progression.Molecular cancer · 2026Article
- Interplay between Epigenetic and Transcription Factors Mediating Drug Resistance via Stem Cells in Breast Cancer.ACS omega · 2025Review
- 13-Docosenamide Enhances Oligodendrocyte Precursor Cell Differentiation via USP33-Mediated Deubiquitination of CNR1 in Chronic Cerebral Hypoperfusion.Neuroscience bulletin · 2025Article
- USP33 Facilitates Retinoblastoma Growth by Deubiquitinating and Stabilizing EPHB2 Protein.Applied biochemistry and biotechnology · 2025Article
- Rat Glioma 101.8 Tissue Strain: Molecular and Morphological Features.International journal of molecular sciences · 2025Article
- Phosphorylation of USP33 by CDK1 stabilizes the mTORC2 component SIN1.Cell death & disease · 2025Article
- USP33 promotes pulmonary microvascular endothelial cell pyroptosis by stabilizing TRAF2 through deubiquitination.Histology and histopathology · 2025Article
- USP33 Regulates DNA Damage Response and Carcinogenesis Through Deubiquitylating and Stabilising p53.Cell proliferation · 2025Article
- USP9X integrates TGF-β and hypoxia signalings to promote ovarian cancer chemoresistance via HIF-2α-maintained stemness.Cell death & disease · 2025Article
- MSK1 promotes colorectal cancer metastasis by increasing Snail protein stability through USP5-mediated Snail deubiquitination.Experimental & molecular medicine · 2025Article
- Involvement of the ubiquitin-proteasome system in the regulation of the tumor microenvironment and progression.Genes & diseases · 2025Review
- A closer look at the role of deubiquitinating enzymes in the Hypoxia Inducible Factor pathway.Biochemical Society transactions · 2024Review
- USP33 is an integrin α6 deubiquitinase and promotes esophageal squamous cell carcinoma cell migration and metastasis.Journal of cancer research and clinical oncology · 2024Article
- Lung-Targeted Lipid Nanoparticle-Delivered siUSP33 Attenuates SARS-CoV-2 Replication and Virulence by Promoting Envelope Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- USP33 facilitates the ovarian cancer progression via deubiquitinating and stabilizing CBX2.Oncogene · 2024Article
- Deubiquitinating enzyme mutagenesis screens identify a USP43-dependent HIF-1 transcriptional response.The EMBO journal · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia regulates tumor angiogenesis, metabolism, and therapeutic response in malignant cancers including glioblastoma, the most lethal primary brain tumor. The regulation of HIF transcriptional factors by the ubiquitin-proteasome system is critical in the hypoxia response, but hypoxia-inducible deubiquitinases that counteract the ubiquitination remain poorly defined. While the activation of ERK1/2 also plays an important role in hypoxia response, the relationship between ERK1/2 activation and HIF regulation remains elusive. Here, we identified USP33 as essential deubiquitinase that stabilizes HIF-2alpha protein in an ERK1/2-dependent manner to promote hypoxia response in cancer cells. USP33 is preferentially induced in glioma stem cells by hypoxia and interacts with HIF-2alpha, leading to its stabilization through deubiquitination. The activation of ERK1/2 upon hypoxia promoted HIF-2alpha phosphorylation, enhancing its interaction with USP33. Silencing of USP33 disrupted glioma stem cells maintenance, reduced tumor vascularization, and inhibited glioblastoma growth. Our findings highlight USP33 as an essential regulator of hypoxia response in cancer stem cells, indicating a novel potential therapeutic target for brain tumor treatment.
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