ArticleThe Journal of biological chemistry2013
c-Cbl, a ubiquitin E3 ligase that targets active β-catenin: a novel layer of Wnt signaling regulation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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Who cites it
44 citing papers in PubMed, 72 citations in OpenAlex.
- ALDH2 inhibits FASN stabilization via the E3 ligase CBL to suppress lipid accumulation and liver cancer development.Biology direct · 2026Article
- Nuclear β-catenin: molecular regulation, challenges and therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- GSK3β Regulates a Novel β-Catenin Degradation Pathway via the GID Complex in Wnt Signaling.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- S-nitrosylation of pVHL regulates βProceedings of the National Academy of Sciences of the United States of America · 2025Article
- A niche driven mechanism determines response and a mutation-independent therapeutic approach for myeloid malignancies.Cancer cell · 2025Article
- IGF1R activates FOXP3-β-catenin signaling to promote breast cancer development.Breast cancer research and treatment · 2025Article
- Inhibition of SCFCommunications biology · 2025Article
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Cbl and Cbl-b ubiquitin ligases are essential for intestinal epithelial stem cell maintenance.iScience · 2024Article
- Article
- Target deubiquitinase OTUB1 as a therapeatic strategy for BLCA via β-catenin/necroptosis signal pathway.International journal of biological sciences · 2024Article
- The role of CBL family ubiquitin ligases in cancer progression and therapeutic strategies.Frontiers in pharmacology · 2024Review
- Human Neuralized is a novel tumour suppressor targeting Wnt/β-catenin signalling in colon cancer.EMBO reports · 2023Article
- Pharmacologic Manipulation of Late SV40 Factor Suppresses Wnt Signaling and Inhibits Growth of Allogeneic and Syngeneic Colon Cancer Xenografts.The American journal of pathology · 2022Article
- S100A16 promotes acute kidney injury by activating HRD1-induced ubiquitination and degradation of GSK3β and CK1α.Cellular and molecular life sciences : CMLS · 2022Article
- Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease.The Journal of clinical investigation · 2022Article
- Review
- 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
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Regulation of transcriptionally active nuclear β-catenin during the Wnt-on phase is crucial to ensure controlled induction of Wnt target genes. Several ubiquitin E3 ligases are known to regulate cytosolic β-catenin during the Wnt-off phase, but little is known about the fate of active nuclear β-catenin in the Wnt-on phase. We now describe ubiquitination of active β-catenin in the Wnt-on phase by a RING finger ubiquitin E3 ligase, Casitas B-lineage lymphoma (c-Cbl) in endothelial cells. c-Cbl binds preferentially to nuclearly active β-catenin in the Wnt-on phase via the armadillo repeat region. Wild-type c-Cbl suppresses and E3 ligase-deficient c-Cbl-70Z increases Wnt signaling. Wnt induces nuclear translocation of c-Cbl where it ubiquitinates nuclear β-catenin. Deletion of the c-Cbl UBA domain abrogates its dimerization, binding to β-catenin, Wnt-induced c-Cbl nuclear translocation, and ubiquitination of nuclear β-catenin. c-Cbl activity inhibits pro-angiogenic Wnt targets IL-8 and VEGF levels and angiogenesis in a β-catenin-dependent manner. This study defines for the first time c-Cbl as a ubiquitin E3 ligase that targets nuclearly active β-catenin in the Wnt-on phase and uncovers a novel layer of regulation of Wnt signaling.
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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.