ArticleCancer cell international2019
SENP1-mediated deSUMOylation of USP28 regulated HIF-1α accumulation and activation during hypoxia response.
Article in Cancer cell international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- [Methyltransferase-like protein 7B promotes glycolysis and malignant progression in papillary thyroid carcinoma cells via the USP28/HIF-1α axis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Article
- Targeting the deubiquitinase USP28 in cancer: navigating context-dependent mechanisms and therapeutic resistance.Frontiers in immunology · 2026Review
- The E3 ubiquitin ligase DTX3L and the deubiquitinase USP28 fine-tune DNA repair through mutual regulation of their protein levels.iScience · 2025Article
- A closer look at the role of deubiquitinating enzymes in the Hypoxia Inducible Factor pathway.Biochemical Society transactions · 2024Review
- SENP1 reduces oxidative stress and apoptosis in renal ischaemia-reperfusion injury by deSUMOylation of HIF-1α.Journal of cellular and molecular medicine · 2024Article
- UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.Molecular and cellular biochemistry · 2024Article
- Structural basis for the bi-specificity of USP25 and USP28 inhibitors.EMBO reports · 2024Article
- DAB2IP inhibits glucose uptake by modulating HIF-1α ubiquitination under hypoxia in breast cancer.Oncogenesis · 2024Article
- The Ubiquitin-Proteasome System in Tumor Metabolism.Cancers · 2023Review
- Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development.Experimental hematology & oncology · 2023Review
- Review
- Article
- iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation.Oncogene · 2022Article
- A positive feedback regulatory loop involving the lncRNA PVT1 and HIF-1α in pancreatic cancer.Journal of molecular cell biology · 2021Article
- Review
- PSF functions as a repressor of hypoxia-induced angiogenesis by promoting mitochondrial function.Cell communication and signaling : CCS · 2021Article
- Article
- The Role of Hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity.International journal of molecular sciences · 2020Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe ubiquitin-specific protease 28 (USP28) is an oncogenic deubiquitinase, which plays a critical role in tumorigenesis via antagonizing the ubiquitination and degradation of tumor suppressor protein FBXW7-mediated oncogenic substrates. USP28 controls hypoxia-dependent angiogenesis and metastasis by preventing FBXW7-dependent hypoxia-inducible transcription factor-1α (HIF-1α) degradation during hypoxia. However, it remains unclear how USP28 activation and HIF-1α signaling are coordinated in response to hypoxia.
methodsThe in vitro deubiquitinating activity assay was used to determine the regulation of USP28 by hypoxia. The co-immunoprecipitation and GST Pull-down assays were used to determine the interaction between USP28 and SENP1. The in vivo deSUMOylation assay was performed to determine the regulation of USP28 by SENP1. The luciferase reporter assay was used to determine the transcriptional activity of HIF-1α.
resultsHere, we report that USP28 is a SUMOylated protein in normoxia with moderate deubiquitinating activity towards HIF-1α in vitro, while hypoxia and HIF-1α activate USP28 through SENP1-mediated USP28 deSUMOylation to further accumulate HIF-1α protein in cells. In agreement with this, a SUMOylation mutant USP28 showed enhanced ability to increase HIF-1α level as well as control the transcriptional activity of HIF-1α.
conclusionCollectively, our results reveal a novel SENP1-USP28-HIF-1α positive feedback loop to maximize the concentration of HIF-1a protein and amplify its downstream effects during hypoxia response.
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