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2017 ; 8
(3
): ä Nephropedia Template TP
gab.com Text
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English Wikipedia
c-Myc-Induced Survivin Is Essential for Promoting
the Notch-Dependent T Cell Differentiation from Hematopoietic Stem Cells
#MMPMID28272325
Haque R
; Song J
; Haque M
; Lei F
; Sandhu P
; Ni B
; Zheng S
; Fang D
; Yang JM
; Song J
Genes (Basel)
2017[Mar]; 8
(3
): ä PMID28272325
show ga
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.