Stimulation of the Ca2+-mediated egr-1 and c-fos expression in murine erythroleukaemia cells by cyclesporin A

A. Schaefer, M. Magócsi, A. Fandrich, H. Marquardt

Research output: Contribution to journalArticle

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Abstract

The Ca2+-induced expression of the primary response genes egr-1 and c-fos was investigated in the murine erythroleukaemia cell line ELM-I-1. Exposure of the cells to the Ca2+-ionophore A23187 led to a rapid transient rise in egr-1 and c-fos mRNA production followed by an increase in Egr-1 and c-Fos protein levels as well as an increase in Egr-1 and activator protein 1 (AP-1) DNA-binding activity. Preincubation of the cells with KN-62, a specific inhibitor of Ca2+/calmodulin-dependent protein kinases, strongly decreased the Ca2+-mediated expression of egr-1 and c-fos. In contrast, treatment with cyclosporin A, which inhibits the Ca2+/calmodulin-dependent protein phosphatase 2B or calcineurin, increased both egr-1 and c-fos mRNA production and the DNA-binding activity of the Egr-1 and AP-1 transcription factors in response to the intracellular Ca+ concentration ([Ca2+](i))-increasing agents A23187 or cyclopiazonic acid. Enhancement of the Ca2+-induced c-fos and egr-1 expression by cyclosporin A was correlated with the capability of this agent to inhibit calcineurin phosphatase activity in ELM-I-1 cells. Studies on the phosphorylation state and DNA-binding activity of the cAMP response element-binding protein (CREB) did not demonstrate an early Ca2+-dependent activation of this transcription factor, suggesting that the regulation of c-fos and egr-1 expression by Ca2+ is not linked to CREB in the haematopoietic ELM-I-1 cells. The results indicate that calcineurin exerts negative regulatory effects on both egr-1 and c-fos expression in murine erythroleukaemia cells, in addition to the calcineurin-mediated down-regulation of c-myb expression observed previously in this cell system. This study therefore emphasizes the important role of calcineurin as a negative modulator of gene expression in certain cell types.

Original languageEnglish
Pages (from-to)505-511
Number of pages7
JournalBiochemical Journal
Volume335
Issue number3
Publication statusPublished - Nov 1 1998

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Leukemia, Erythroblastic, Acute
Calcineurin
Cyclic AMP Response Element-Binding Protein
KN 62
Transcription Factor AP-1
Cyclosporine
DNA
Transcription Factors
Calcimycin
Proto-Oncogene Proteins c-fos
Calcium-Calmodulin-Dependent Protein Kinases
Messenger RNA
Phosphorylation
Ionophores
Calmodulin
Gene expression
Modulators
Genes
Chemical activation
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Stimulation of the Ca2+-mediated egr-1 and c-fos expression in murine erythroleukaemia cells by cyclesporin A. / Schaefer, A.; Magócsi, M.; Fandrich, A.; Marquardt, H.

In: Biochemical Journal, Vol. 335, No. 3, 01.11.1998, p. 505-511.

Research output: Contribution to journalArticle

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