ArticleOncogene2010
Differential subcellular localization regulates c-Cbl E3 ligase activity upon Notch3 protein in T-cell leukemia.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- MAML1 drives Notch and Hedgehog oncogenic pathways by inhibiting Itch activity in triple-negative breast cancer.Cell death and differentiation · 2026Article
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- microRNA-155-5p initiates childhood acute lymphoblastic leukemia by regulating the IRF4/CDK6/CBL axis.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- E3 ubiquitin ligases in the acute leukemic signaling pathways.Frontiers in physiology · 2022Review
- The role of ubiquitination in spinal and bulbar muscular atrophy.Frontiers in molecular neuroscience · 2022Review
- 5FU/Oxaliplatin-Induced Jagged1 Cleavage Counteracts Apoptosis Induction in Colorectal Cancer: A Novel Mechanism of Intrinsic Drug Resistance.Frontiers in oncology · 2022Article
- Multifaceted regulation of Notch signaling by glycosylation.Glycobiology · 2021Review
- Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response.Oncogenesis · 2020Article
- In vivo and in vitro inhibition of osteosarcoma growth by the pan Bcl-2 inhibitor AT-101.Investigational new drugs · 2020Article
- Wnt, Notch, and TGF-β Pathways Impinge on Hedgehog Signaling Complexity: An Open Window on Cancer.Frontiers in genetics · 2019Review
- Notch3 Targeting: A Novel Weapon against Ovarian Cancer Stem Cells.Stem cells international · 2019Review
- Adenosine A2A Receptor Stimulation Inhibits TCR-Induced Notch1 Activation in CD8+T-Cells.Frontiers in immunology · 2019Article
- Notch Signaling Activation as a Hallmark for Triple-Negative Breast Cancer Subtype.Journal of oncology · 2019Review
- Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation.Oncogene · 2018Article
- NOTCH3 inactivation increases triple negative breast cancer sensitivity to gefitinib by promoting EGFR tyrosine dephosphorylation and its intracellular arrest.Oncogenesis · 2018Article
- Maml1 acts cooperatively with Gli proteins to regulate sonic hedgehog signaling pathway.Cell death & disease · 2017Article
- Prolyl-isomerase Pin1 controls Notch3 protein expression and regulates T-ALL progression.Oncogene · 2016Article
- The Novel PKCθ from Benchtop to Clinic.Journal of immunology research · 2015Review
- Notch3/Jagged1 circuitry reinforces notch signaling and sustains T-ALL.Neoplasia (New York, N.Y.) · 2014Article
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch3 and pTalpha signaling events are essential for T-cell leukemogenesis and characterize murine and human T-cell acute lymphoblastic leukemia. Genetic ablation of pTalpha expression in Notch3 transgenic mice abrogates tumor development, indicating that pTalpha signaling is crucial to the Notch3-mediated leukemogenesis. Here we report a novel direct interaction between Notch3 and pTalpha. This interaction leads to the recruitment and persistence of the E3 ligase protein c-Cbl to the lipid rafts in Notch3-IC transgenic thymocytes. Conversely, deletion of pTalpha in Notch3 transgenic mice leads to cytoplasmic retention of c-Cbl that targets Notch3 protein to the proteasomal-degradative pathway. It appears that protein kinase C theta (PKCtheta), by regulating tyrosine and serine phosphorylation of Cbl, is able to control its function. We report here that the increased Notch3-IC degradation correlates with higher levels of c-Cbl tyrosine phosphorylation in Notch3-IC/pTalpha(-/-) double-mutant thymocytes, which also display a decreased PKCtheta activity. Our data indicate that pTalpha/pre-T-cell receptor is able to regulate the different subcellular localization of c-Cbl and, by regulating PKCtheta activity, is also able to influence its ubiquitin ligase activity upon Notch3 protein.
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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.