ArticleThe Journal of biological chemistry2015
The c-Cbl ubiquitin ligase regulates nuclear β-catenin and angiogenesis by its tyrosine phosphorylation mediated through the Wnt signaling pathway.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Pooled it
- Targeting β-catenin: PROTACs and precision degraders for Wnt-driven cancers.Frontiers in oncology · 2026Review
- PTPN22 Dephosphorylates CBL to Inhibit PD-L1 Ubiquitination and Drive Immunosuppression in Renal Cell Carcinoma.International journal of biological sciences · 2026Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Tissue engineering approaches for dental pulp regeneration: The development of novel bioactive materials using pharmacological epigenetic inhibitors.Bioactive materials · 2024Review
- Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.iScience · 2024Article
- RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation.British journal of cancer · 2024Article
- Roles of ubiquitination in the crosstalk between tumors and the tumor microenvironment (Review).International journal of oncology · 2022Review
- Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease.The Journal of clinical investigation · 2022Article
- E3 ligase c-Cbl regulates intestinal inflammation through suppressing fungi-induced noncanonical NF-κB activation.Science advances · 2021Article
- Breakdown of Filamentous Myofibrils by the UPS-Step by Step.Biomolecules · 2021Review
- Zebrafish Cancer Predisposition Models.Frontiers in cell and developmental biology · 2021Review
- Review
- Cerebral arteriopathy associated with heterozygous variants in the casitas B-lineage lymphoma gene.Neurology. Genetics · 2020Article
- Haploinsufficiency of Casitas B-Lineage Lymphoma Augments the Progression of Colon Cancer in the Background of Adenomatous Polyposis Coli Inactivation.The American journal of pathology · 2020Article
- c-Cbl targets PD-1 in immune cells for proteasomal degradation and modulates colorectal tumor growth.Scientific reports · 2019Article
- Review
- Review
- Role of ADTRP (Androgen-Dependent Tissue Factor Pathway Inhibitor Regulating Protein) in Vascular Development and Function.Journal of the American Heart Association · 2018Article
- c-Cbl Expression Correlates with Human Colorectal Cancer Survival and Its Wnt/β-Catenin Suppressor Function Is Regulated by Tyr371 Phosphorylation.The American journal of pathology · 2018Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Wnt signaling plays important roles in both the tumor-induced angiogenesis and tumorigenesis through the transcriptionally active nuclear β-catenin. Recently, c-Cbl was identified as a unique E3 ubiquitin ligase targeting the active nuclear β-catenin. However, little is known about the molecular mechanisms by which c-Cbl regulates ubiquitination and degradation of active β-catenin. Here, we demonstrate that Wnt activation promotes the phosphorylation of c-Cbl at tyrosine 731(Tyr-731), which increases c-Cbl dimerization and binding to β-catenin. Tyr-731 phosphorylation and dimerization mediate c-Cbl nuclear translocation and lead to the degradation of nuclearly active β-catenin in the Wnt-on phase. c-Cbl activation also inhibits expression of the pro-angiogenic Wnt targets, IL-8 and VEGF. Phospho-Tyr-731-inactive mutant c-Cbl (Y731F) enhances and phosphomimetic mutant c-Cbl (Y731E) suppresses angiogenesis in zebrafish. Taken together, we have identified a novel mechanism for the regulation of active nuclear β-catenin by c-Cbl and its critical role in angiogenesis. This mechanism can be further explored to modulate both the pathological angiogenesis and the tumorigenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.