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

Konstantin Levay, Vladlen Z Slepak

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2672-2683
Number of pages12
JournalJournal of Clinical Investigation
Volume117
Issue number9
DOIs
StatePublished - Sep 4 2007

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K562 Cells
Proto-Oncogene Protein c-ets-1
Gene Expression
Megakaryocytes
MAP Kinase Signaling System
Surface Antigens
Hematopoietic Stem Cells
RNA Interference
Proteins
Up-Regulation
Cell Proliferation
Cell Line
Genes

ASJC Scopus subject areas

  • Medicine(all)

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Tescalcin is an essential factor in megakaryocytic differentiation associated with Ets family gene expression. / Levay, Konstantin; Slepak, Vladlen Z.

In: Journal of Clinical Investigation, Vol. 117, No. 9, 04.09.2007, p. 2672-2683.

Research output: Contribution to journalArticle

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