c-Myc-InducedSurvivinIsEssentialforPromoting theNotch-DependentTCellDifferentiationfrom HematopoieticStemCells.
- Additional Document Info
- View All
Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c-Myc is a key mediator of the Notch signaling-regulated T cell differentiation. In a well-established in vitro differentiation model of T lymphocytes from hematopoietic stem cells, we showed that Notch1 and 4 directly promoted c-Myc expression; dominant-negative (DN) c-Myc inhibited early T cell differentiation. Moreover, the c-Myc expression activated by Notch signaling increased the expression of survivin, an inhibitor of apoptosis (IAP) protein. We further demonstrated that over-expression of c-Myc increased the abundance of survivin and the T cell differentiation thereof, whereas dn c-Myc reduced survivin levels and concomitantly retarded the differentiation. The c-Myc-dependent survivin induction is functionally germane, because Notch-dependent T cell differentiation was canceled by the depletion of survivin. These results identify both c-Myc and survivin as important mediators of the Notch signaling-regulated differentiation of T lymphocytes from hematopoietic stem cells.
author list (cited authors)
Haque, R., Song, J., Haque, M., Lei, F., Sandhu, P., Ni, B., ... Song, J.
complete list of authors
Haque, Rizwanul||Song, Jianyong||Haque, Mohammad||Lei, Fengyang||Sandhu, Praneet||Ni, Bing||Zheng, Songguo||Fang, Deyu||Yang, Jin-Ming||Song, Jianxun