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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD34 / metabolism
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Bone Marrow Cells / metabolism
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Cell Adhesion
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Cell Differentiation*
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Cell Line
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Cell Proliferation / drug effects
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Enzyme Activation
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation*
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Humans
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Integrins / metabolism
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Megakaryocytes / cytology*
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Megakaryocytes / metabolism*
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Phorbol 12,13-Dibutyrate / pharmacology
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Platelet Glycoprotein GPIb-IX Complex / metabolism
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Platelet Membrane Glycoproteins / metabolism
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Polyploidy
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Telomerase / classification*
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Telomerase / genetics*
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Telomerase / metabolism
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Transcription, Genetic / genetics
Substances
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Antigens, CD34
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Calcium-Binding Proteins
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Integrins
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Platelet Glycoprotein GPIb-IX Complex
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Platelet Membrane Glycoproteins
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TESC protein, human
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glycoprotein receptor GPIb-IX
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Phorbol 12,13-Dibutyrate
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Extracellular Signal-Regulated MAP Kinases
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Telomerase