ArticleCell reports2012
E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity.
Article in Cell reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- NEDD4 Promotes Sertoli Cell Proliferation and Adult Leydig Cell Differentiation in the Murine Testis.Endocrinology · 2025Article
- K27-linked RORγt ubiquitination by Nedd4 potentiates Th17-mediated autoimmunity.Journal of biomedical science · 2025Article
- Reprogramming of tumor-associated macrophages via NEDD4-mediated CSF1R degradation by targeting USP18.Cell reports · 2023Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- The RING finger protein family in health and disease.Signal transduction and targeted therapy · 2022Review
- Overproduction of IFNγ by Cbl-b-Deficient CD8+ T Cells Provides Resistance against Regulatory T Cells and Induces Potent Antitumor Immunity.Cancer immunology research · 2022Article
- Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2021Review
- HECT E3 Ubiquitin Ligase Nedd4 Is Required for Antifungal Innate Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- CD5 signalosome coordinates antagonist TCR signals to control the generation of Treg cells induced by foreign antigens.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia.The Journal of experimental medicine · 2020Article
- Soluble PD-1: Predictive, Prognostic, and Therapeutic Value for Cancer Immunotherapy.Frontiers in immunology · 2020Review
- Role of Ubiquitination in PTEN Cellular Homeostasis and Its Implications in GB Drug Resistance.Frontiers in oncology · 2020Review
- The many substrates and functions of NEDD4-1.Cell death & disease · 2019Review
- Review
- Regulation of immune responses by E3 ubiquitin ligase Cbl-b.Cellular immunology · 2019Review
- Suppressed expression of Cbl-b by NF-κB mediates icotinib resistance in EGFR-mutant non-small-cell lung cancer.Cell biology international · 2019Article
- Turning the Tide Against Regulatory T Cells.Frontiers in oncology · 2019Review
- CBLB Constrains Inactivated Vaccine-Induced CD8Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Lys63-polyubiquitination by the E3 ligase casitas B-lineage lymphoma-b (Cbl-b) modulates peripheral regulatory T cell tolerance in patients with systemic lupus erythematosus.Clinical and experimental immunology · 2018Article
- Modulating Host Signaling Pathways to Promote Resistance to Infection byFrontiers in cellular and infection microbiology · 2017Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
E3 ubiquitin ligase Cbl-b plays a crucial role in T cell activation and tolerance induction. However, the molecular mechanism by which Cbl-b inhibits T cell activation remains unclear. Here, we report that Cbl-b does not inhibit PI3K but rather suppresses TCR/CD28-induced inactivation of Pten. The elevated Akt activity in Cbl-b(-/-) T cells is therefore due to heightened Pten inactivation. Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination. Consistent with this finding, introducing Nedd4 deficiency into Cbl-b(-/-) mice abrogates hyper-T cell responses caused by the loss of Cbl-b. Hence, our data demonstrate that Cbl-b inhibits T cell activation by suppressing Pten inactivation independently of its ubiquitin ligase activity.
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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.