ArticleThe EMBO journal2005
Loss of c-Cbl RING finger function results in high-intensity TCR signaling and thymic deletion.
Article in The EMBO journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- The ubiquitin ligase CBL and Fas-associated factor 2 cooperate to regulate the innate immune response to M. tuberculosis.PLoS pathogens · 2026Article
- Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function.Nature immunology · 2026Article
- Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.iScience · 2026Review
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- Lysosomal transmembrane protein 5: Impact on immune cell function and implications for immune-related deficiencies.Heliyon · 2024Review
- The balance between antiviral and antibacterial responses duringbioRxiv : the preprint server for biology · 2024Article
- Article
- LFA-1 signals to promote actin polymerization and upstream migration in T cells.Journal of cell science · 2020Article
- CD5 dynamically calibrates basal NF-κB signaling in T cells during thymic development and peripheral activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Crk adaptor proteins mediate actin-dependent T cell migration and mechanosensing induced by the integrin LFA-1.Science signaling · 2018Article
- VAV1-Cre mediated hematopoietic deletion of CBL and CBL-B leads to JMML-like aggressive early-neonatal myeloproliferative disease.Oncotarget · 2016Article
- Article
- Cell regulation by phosphotyrosine-targeted ubiquitin ligases.Molecular and cellular biology · 2015Review
- Loss of Cbl and Cbl-b ubiquitin ligases abrogates hematopoietic stem cell quiescence and sensitizes leukemic disease to chemotherapy.Oncotarget · 2015Article
- Loss of Cbl-PI3K interaction in mice prevents significant bone loss following ovariectomy.Bone · 2014Article
- Article
- CBL linker region and RING finger mutations lead to enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling via elevated levels of JAK2 and LYN.The Journal of biological chemistry · 2013Article
- Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases.Biochimica et biophysica acta · 2013Review
- Article
- The E3 ligase c-Cbl regulates dendritic cell activation.EMBO reports · 2011Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling from the T-cell receptor (TCR) in thymocytes is negatively regulated by the RING finger-type ubiquitin ligase c-Cbl. To further investigate this regulation, we generated mice with a loss-of-function mutation in the c-Cbl RING finger domain. These mice exhibit complete thymic deletion by young adulthood, which is not caused by a developmental block, lack of progenitors or peripheral T-cell activation. Rather, this phenotype correlates with greatly increased expression of the CD5 and CD69 activation markers and increased sensitivity to anti-CD3-induced cell death. Thymic loss contrasts the normal fate of the c-Cbl-/- thymus, even though thymocytes from both mutant mice show equivalent enhancement in proximal TCR signaling, Erk activation and calcium mobilization. Remarkably, only the RING finger mutant thymocytes show prominent TCR-directed activation of Akt. We show that the mutant c-Cbl protein itself is essential for activating this pathway by recruiting the p85 regulatory subunit of PI 3-kinase. This study provides a unique model for analyzing high-intensity TCR signals that cause thymocyte deletion and highlights multiple roles of c-Cbl in regulating this process.
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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.