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- W2094328127 abstract "Notch3 and pTα signaling events are essential for T-cell leukemogenesis and characterize murine and human T-cell acute lymphoblastic leukemia. Genetic ablation of pTα expression in Notch3 transgenic mice abrogates tumor development, indicating that pTα signaling is crucial to the Notch3-mediated leukemogenesis. Here we report a novel direct interaction between Notch3 and pTα. 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 pTα 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 θ (PKCθ), 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/pTα−/− double-mutant thymocytes, which also display a decreased PKCθ activity. Our data indicate that pTα/pre-T-cell receptor is able to regulate the different subcellular localization of c-Cbl and, by regulating PKCθ activity, is also able to influence its ubiquitin ligase activity upon Notch3 protein." @default.
- W2094328127 created "2016-06-24" @default.
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- W2094328127 date "2009-12-07" @default.
- W2094328127 modified "2023-09-25" @default.
- W2094328127 title "Differential subcellular localization regulates c-Cbl E3 ligase activity upon Notch3 protein in T-cell leukemia" @default.
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- W2094328127 doi "https://doi.org/10.1038/onc.2009.446" @default.
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