ArticleOncogene2015
RSUME inhibits VHL and regulates its tumor suppressor function.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- The emerging roles of SUMOylation in the tumor microenvironment and therapeutic implications.Experimental hematology & oncology · 2023Review
- Impact of RSUME Actions on Biomolecular Modifications in Physio-Pathological Processes.Frontiers in endocrinology · 2022Review
- VHL-P138R and VHL-L163R Novel Variants: Mechanisms of VHL Pathogenicity Involving HIF-Dependent and HIF-Independent Actions.Frontiers in endocrinology · 2022Article
- Review
- Lessons from Comparison of Hypoxia Signaling in Plants and Mammals.Plants (Basel, Switzerland) · 2021Review
- Review
- von Hippel-Lindau mutants in renal cell carcinoma are regulated by increased expression of RSUME.Cell death & disease · 2019Article
- LSD1 inhibition suppresses the growth of clear cell renal cell carcinomaActa pharmaceutica Sinica. B · 2019Article
- Progress of small ubiquitin-related modifiers in kidney diseases.Chinese medical journal · 2019Review
- Knockdown of RWD domain containing 3 inhibits the malignant phenotypes of glioblastoma cells via inhibition of phosphoinositide 3-kinase/protein kinase B signaling.Experimental and therapeutic medicine · 2018Article
- A compendium of proteins that interact with HIF-1α.Experimental cell research · 2017Article
- Forkhead Transcription Factor 3a (FOXO3a) Modulates Hypoxia Signaling via Up-regulation of the von Hippel-Lindau Gene (VHL).The Journal of biological chemistry · 2016Article
- RSUME is implicated in tumorigenesis and metastasis of pancreatic neuroendocrine tumors.Oncotarget · 2016Article
- Function and Structure of the RWD Domain.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic mutations or loss of von Hippel-Lindau (pVHL) happen in the majority of VHL disease tumors, which present a constitutively active Hypoxia Inducible Factor (HIF), essential for tumor growth. Recently described mechanisms for pVHL modulation shed light on the open question of the HIF/pVHL pathway regulation. The aim of the present study was to determine the molecular mechanism by which RSUME stabilizes HIFs, by studying RSUME effect on pVHL function and to determine the role of RSUME on pVHL-related tumor progression. We determined that RSUME sumoylates and physically interacts with pVHL and negatively regulates the assembly of the complex between pVHL, Elongins and Cullins (ECV), inhibiting HIF-1 and 2α ubiquitination and degradation. We found that RSUME is expressed in human VHL tumors (renal clear-cell carcinoma (RCC), pheochromocytoma and hemangioblastoma) and by overexpressing or silencing RSUME in a pVHL-HIF-oxygen-dependent degradation stability reporter assay, we determined that RSUME is necessary for the loss of function of type 2 pVHL mutants. The functional RSUME/pVHL interaction in VHL-related tumor progression was further confirmed using a xenograft assay in nude mice. RCC clones, in which RSUME was knocked down and express either pVHL wt or type 2 mutation, have an impaired tumor growth, as well as HIF-2α, vascular endothelial growth factor A and tumor vascularization diminution. This work shows a novel mechanism for VHL tumor progression and presents a new mechanism and factor for targeting tumor-related pathologies with pVHL/HIF altered function.
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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.