Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression
Konstantin Levay, Vladlen Z. Slepak
Konstantin Levay, Vladlen Z. Slepak
Published September 4, 2007
Citation Information: J Clin Invest. 2007;117(9):2672-2683. https://doi.org/10.1172/JCI27465.
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Research Article Hematology

Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression

Abstract

We show here that the process of megakaryocytic differentiation requires the presence of the recently discovered protein tescalcin. Tescalcin is dramatically upregulated during the differentiation and maturation of primary megakaryocytes or upon PMA-induced differentiation of K562 cells. This upregulation requires sustained signaling through the ERK pathway. Overexpression of tescalcin in K562 cells initiates events of spontaneous megakaryocytic differentiation, such as expression of specific cell surface antigens, inhibition of cell proliferation, and polyploidization. Conversely, knockdown of this protein in primary CD34+ hematopoietic progenitors and cell lines by RNA interference suppresses megakaryocytic differentiation. In cells lacking tescalcin, the expression of Fli-1, Ets-1, and Ets-2 transcription factors, but not GATA-1 or MafB, is blocked. Thus, tescalcin is essential for the coupling of ERK cascade activation with the expression of Ets family genes in megakaryocytic differentiation.

Authors

Konstantin Levay, Vladlen Z. Slepak

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Figure 5

Tescalcin knockdown inhibits the expression of MK-specific marker GPIIb.

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Tescalcin knockdown inhibits the expression of MK-specific marker GPIIb....
(A) HEL-Ctrl(–) and HEL-Tsc(–) cells were cultured in the absence or presence of 10 nM PMA for 72 hours and then analyzed for the cell surface expression of GPIIb (CD41), α4 (CD49d), and α5 (CD49e) integrins by FACS. (B) K562-Ctrl(–) and K562-Tsc(–) cells were cultured in the absence or presence of PMA for 72 hours and analyzed for the cell surface expression of GPIIb by FACS. (C) HEL-Ctrl(–) and HEL-Tsc(–) cells were cultured in the absence or presence of PMA for 72 hours and then subjected to Western blot analysis of the total expression of GPIIb. β-Actin was used as a loading control. (D) K562 cells were analyzed as described in C.