ERK pathway inhibitor U0126 induces gamma-globin expression in erythroid cells

R. L. McElveen, T. F. Lou, K. Reese, S. Xia, B. S. Baliga, Betty Sue Pace

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Fetal hemoglobin (HbF) induction is an effective approach to improve clinical symptoms in sickle cell disease. Understanding molecular mechanisms for gamma-gene re-activation will aid efforts to design lead compounds. A potential inhibitory role for the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway in gamma-gene expression has been suggested recently. Therefore, we determined the ability of U0126, a selective inhibitor of MEK1/2 the upstream activators of ERK, to re-activate gamma-globin expression. K562 stable lines over-expressing constitutively active MEK1 were established. A significant increase in ERK phosphorylation was observed and gamma-gene expression was silenced concomitantly, however U0126 attenuated this effect. Studies in human erythroid progenitors confirmed the ability of U0126 to induce HbF. Cellular mechanisms for the inhibitory role of ERK signaling in drug-mediated HbF induction will be discussed.

Original languageEnglish (US)
Pages (from-to)215-227
Number of pages13
JournalCellular and Molecular Biology
Volume51
Issue number2
StatePublished - Sep 5 2005
Externally publishedYes

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Keywords

  • ERK
  • Fetal hemoglobin
  • Gamma-globin
  • Sickle cell disease
  • U0126

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

McElveen, R. L., Lou, T. F., Reese, K., Xia, S., Baliga, B. S., & Pace, B. S. (2005). ERK pathway inhibitor U0126 induces gamma-globin expression in erythroid cells. Cellular and Molecular Biology, 51(2), 215-227.