1. PKC?mediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia.
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Felli, Maria Pia, Vacca, Alessandra, Calce, Angelica, Bellavia, Diana, Campese, Antonio F., Grillo, Rita, Di Giovine, Monica, Checquolo, Saula, Talora, Claudio, Palermo, Rocco, Di Mario, Giuseppina, Frati, Luigi, Gulino, Alberto, and Screpanti, Isabella
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LEUCOCYTOSIS , *PRELEUKEMIA , *TRANSGENIC mice , *PHOSPHOTRANSFERASES , *CANCER , *ANEMIA , *LYMPHOMAS - Abstract
Protein kinase (PK)C?is a critical regulator of mature T-cell activation and proliferation, being implicated in TCR-triggered nuclear factor (NF)-?B activation and providing important survival signals to leukemic T cells. We previously showed that overexpression of pTa/pre-TCR and constitutive activation of NF-?B characterize the T-cell leukemia/lymphoma developing in Notch3-IC transgenic mice. We report here that PKC?is a downstream target of Notch3 signaling and that its activation and membrane translocation require a functional pre-TCR in order to trigger NF-?B activation in thymocytes and lymphoma cells of transgenic mice. Furthermore, deletion of PKC?in Notch3-IC transgenic mice reduces the incidence of leukemia, correlating with decreased NF-?B activation. This paper therefore suggests that PKC?mediates the activation of NF-?B by pre-TCR in immature thymocytes and contributes to the development of Notch3-dependent T-cell lymphoma.Oncogene (2005) 24, 992-1000. doi:10.1038/sj.onc.1208302 Published online 13 December 2004 [ABSTRACT FROM AUTHOR]
- Published
- 2005
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