ArticleOncotarget2016
USP9X destabilizes pVHL and promotes cell proliferation.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Hypoxia Increases Cardiac Proteasomal Activity and Differentially Modulates Cullin-RING E3 Ligases in the Naked Mole-RatMuscles (Basel, Switzerland) · 2026Article
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- 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
- HSPA12A stimulates "Smurf1-Hif1α-aerobic glycolysis" axis to promote proliferation of renal tubular epithelial cells after hypoxia/reoxygenation injury.Cell stress & chaperones · 2024Article
- HSPA12A maintains aerobic glycolytic homeostasis and Histone3 lactylation in cardiomyocytes to attenuate myocardial ischemia/reperfusion injury.JCI insight · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Critical role of VHL/BICD2/STAT1 axis in crystal-associated kidney disease.Cell death & disease · 2023Article
- Research Progress in Function and Regulation of E3 Ubiquitin Ligase SMURF1.Current medical science · 2023Review
- Generation of a live attenuated influenza A vaccine by proteolysis targeting.Nature biotechnology · 2022Article
- Ubiquitin Specific Protease USP48 Destabilizes NF-κB/p65 in Retinal Pigment Epithelium Cells.International journal of molecular sciences · 2022Article
- USP33 deubiquitinates and stabilizes HIF-2alpha to promote hypoxia response in glioma stem cells.The EMBO journal · 2022Article
- Enhanced glucose metabolism through activation of HIF-1α covers the energy demand in a rat embryonic heart primordium after heartbeat initiation.Scientific reports · 2022Article
- SHARPIN regulates the development of clear cell renal cell carcinoma by promoting von Hippel-Lindau protein ubiquitination and degradation.Cancer science · 2021Article
- Targeting the Ubiquitin Signaling Cascade in Tumor Microenvironment for Cancer Therapy.International journal of molecular sciences · 2021Review
- Deubiquitylase OTUD6B Governs pVHL Stability in an Enzyme-Independent Manner and Suppresses Hepatocellular Carcinoma Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL.The Journal of cell biology · 2019Article
- Involvement of E3 Ligases and Deubiquitinases in the Control of HIF-α Subunit Abundance.Cells · 2019Review
- NovelHuman genome variation · 2019Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous mutations of the Von Hippel-Lindau (VHL) gene have been reported to cause dysfunction of VHL protein (pVHL) and lead to processes related to tumor progression. pVHL acts as an E3 ligase and degrades downstream targets, such as hypoxia-inducible transcription factor (HIF) which is essential for tumor growth. Previous studies reported reduction of VHL protein, rather than mRNA in VHL-related tumor patients, suggesting that instability of the pVHL protein itself is a primary cause of dysfunction. Regulation of pVHL stability has therefore been a major focus of research. We report that ubiquitin-specific protease 9X (USP9X), which is a deubiquitinase binds and promotes degradation of both wild-type and mutants of pVHL that retain E3 ligase function, thus activating the HIF pathway. USP9X degrades pVHL through protection of its substrate, the newly identified pVHL E3 ligase Smurf1. In addition, USP9X activates glycolysis and promotes cell proliferation through pVHL. Treatment with a USP9X inhibitor shows an effect similar to USP9X knockdown in pVHL induction, and suppresses HIF activity. Our findings demonstrate that USP9X is a novel regulator of pVHL stability, and USP9X may be a therapeutic target for treatment of VHL-related tumors.
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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.