ArticleGenes & development2015
WSB1 promotes tumor metastasis by inducing pVHL degradation.
Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 83 citations in OpenAlex.
- WSB1-Mediated PSMA Ubiquitination Promotes Enzalutamide-Induced Neuroendocrine-like Transition in Patient-Derived Prostate Cancer Spheroids.International journal of molecular sciences · 2026Article
- Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function.Cell · 2026Article
- AMPK-activated BAP1 regulates pVHL stability and tumor-suppressive functions.Cell death and differentiation · 2026Article
- Proteostasis sustains T cell differentiation potential and tumor-infiltrating lymphocyte function.bioRxiv : the preprint server for biology · 2026Article
- WSB1 is dispensable for mouse spermatogenesis and male fertility.American journal of translational research · 2026Article
- Okanin Suppresses the Growth of Colorectal Cancer Cells by Targeting at Peroxiredoxin 5.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- UHRF1-mediated HIF-1α stabilization promotes ovarian cancer through metabolic reprogramming and angiogenesis.Cell death & disease · 2025Article
- Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors.Molecular medicine reports · 2025Article
- S-nitrosylation of pVHL regulates βProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting the WSB2-NOXA axis in cancer cells for enhanced sensitivity to BCL-2 family protein inhibitors.eLife · 2025Article
- UFMylation maintains tumor suppressor pVHL stability by activating the deubiquitinase BAP1.Science advances · 2025Article
- Identification and validation of a thirteen-gene signature based on ubiquitin related genes in cervical cancer.Discover oncology · 2025Article
- Ubiquitination and ALL: Identifying FBXO8 as a prognostic biomarker and therapeutic target.Frontiers in immunology · 2025Article
- WSB1 promotes prostate cancer malignancy through OTUD4-mediated ISOC2 stabilization and P16INK4a suppression.American journal of cancer research · 2025Article
- Article
- Pharmacological induction of the hypoxia response pathway in Huh7 hepatoma cells limits proliferation but increases resilience under metabolic stress.Cellular and molecular life sciences : CMLS · 2024Article
- WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination.Nucleic acids research · 2024Article
- WSB1, as an E3 ligase, restrains myocardial ischemia-reperfusion injury by activating β-catenin signaling via promoting GSK3β ubiquitination.Molecular medicine (Cambridge, Mass.) · 2024Article
- Revisiting the role of hypoxia-inducible factors and nuclear factor erythroid 2-related factor 2 in regulating macrophage inflammation and metabolism.Frontiers in cellular and infection microbiology · 2024Review
- Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
The von Hippel-Lindau tumor suppressor pVHL is an E3 ligase that targets hypoxia-inducible factors (HIFs). Mutation of VHL results in HIF up-regulation and contributes to processes related to tumor progression such as invasion, metastasis, and angiogenesis. However, very little is known with regard to post-transcriptional regulation of pVHL. Here we show that WD repeat and SOCS box-containing protein 1 (WSB1) is a negative regulator of pVHL through WSB1's E3 ligase activity. Mechanistically, WSB1 promotes pVHL ubiquitination and proteasomal degradation, thereby stabilizing HIF under both normoxic and hypoxic conditions. As a consequence, WSB1 up-regulates the expression of HIF-1α's target genes and promotes cancer invasion and metastasis through its effect on pVHL. Consistent with this, WSB1 protein level negatively correlates with pVHL level and metastasis-free survival in clinical samples. This work reveals a new mechanism of pVHL's regulation by which cancer acquires invasiveness and metastatic tendency.
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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.