ArticleCell death & disease2022
Deubiquitylase OTUD6B stabilizes the mutated pVHL and suppresses cell migration in clear cell renal cell carcinoma.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Targeting the OTU family: a core therapeutic strategy for reshaping the immunosuppressive microenvironment and reversing drug resistance in HCC by coordinating the autophagy-ferroptosis balance.Cell death discovery · 2026Review
- Proximity proteomics reveals OTUD6B regulation of stress granule dynamics through coalescence with VCP/p97.Cell death & disease · 2026Article
- Research progress of OTUD7B: from structural function and disease mechanisms to clinical translation.Frontiers in immunology · 2026Review
- OTU deubiquitinases in disease: roles and targeting.Trends in molecular medicine · 2026Review
- Dysregulation of the ubiquitin-proteasome system in von Hippel-Lindau syndrome: molecular insights and clinical perspectives.Clinical and experimental medicine · 2025Review
- ATRA upregulates OTUD6B to recruit CD8Cell death & disease · 2025Article
- Roles of E3 ubiquitin ligases and deubiquitinating enzymes in renal cell carcinoma.Frontiers in oncology · 2025Review
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Alteration of chromatin states perturb the transcription regulation of gene during hydronephrosis.Frontiers in genetics · 2025Article
- Dissecting the dual role of OTU family proteins in tumor progression and immune escape.Frontiers in immunology · 2025Review
- Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response.Oncology research · 2025Review
- OTU deubiquitinases in cancer pathogenesis and precision therapy.American journal of cancer research · 2025Review
- ESRP1-mediated biogenesis of circPTPN12 inhibits hepatocellular carcinoma progression by PDLIM2/ NF-κB pathway.Molecular cancer · 2024Article
- The deubiquitinating protein OTUD6B promotes lung adenocarcinoma progression by stabilizing RIPK1.Biology direct · 2024Article
- Friend or foe? Reciprocal regulation between E3 ubiquitin ligases and deubiquitinases.Biochemical Society transactions · 2024Review
- Spotlights on ubiquitin-specific protease 12 (USP12) in diseases: from multifaceted roles to pathophysiological mechanisms.Journal of translational medicine · 2023Review
- The Tumor Immune Microenvironment in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2023Review
- VHL-HIF-2α axis-induced SEMA6A upregulation stabilized β-catenin to drive clear cell renal cell carcinoma progression.Cell death & disease · 2023Article
- Review
- Loss of OTUD6B Stimulates Angiogenesis and Promotes Diabetic Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Von Hippel-Lindau (VHL) is an important tumor suppressor, and its inactivation is a hallmark of inherited VHL disease and most sporadic clear cell renal cell carcinoma (ccRCC). VHL protein (pVHL) with missense point mutations are unstable and degraded by the proteasome because of the disruption of elongin binding. Deubiquitylase ovarian tumor domain-containing 6B (OTUD6B) had been documented to couple pVHL and elongin B to form stable VHL - elonginB - elonginC complex, which protects pVHL from degradation. However, whether OTUD6B governs the stability of pVHL wild type and the missense mutants in ccRCC remains largely elusive. Here, we reported that low OTUD6B level predicted poorer survival in ccRCC patients with VHL missense mutation, but not frameshift deletion and nonsense mutation. OTUD6B is able to interact with wild type pVHL and tumor-derived pVHL missense mutants, except for pVHL I151T, and decrease their ubiquitylation and proteasomal degradation in ccRCC cells. Functionally, we revealed that OTUD6B depletion enhanced cell migration and HIF-2α level in ccRCC cells in a pVHL dependent manner. In addition, OTUD6B depletion reduced the inhibitory effects of ectopic pVHL missense mutants on cell migration and HIF-2α level, except for pVHL I151T. Thus, we speculated that I151 residue might be one of key sites of pVHL binding to OTUD6B. These results suggested that OTUD6B is an important regulator for the stability of pVHL missense mutants, which provides a potential therapeutic strategy for ccRCC with VHL mutations.
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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.