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Mitogen- and stress-activated protein kinase 1 is critical for interleukin-1-induced, CREB-mediated, c-fos gene expression in keratinocytes

Oncogene volume 25, pages 4449–4457 (2006)Cite this article

Abstract

c-fos, which encodes a transcription factor of the AP-1 family, is a prototypical immediate-early gene induced by a number of proinflammatory cytokines including interleukin-1 (IL-1), the latter being an important regulator of skin homeostasis. Using the human keratinocyte cell line HaCaT as an in vitro model, we dissected the molecular pathways leading to IL-1-induced c-fos gene induction. Phosphorylation of the transcription factor cAMP response element binding protein (CREB) at Ser133 was found to be essential for IL-1-induced c-fos gene induction and was closely paralleled by protein kinase A (PKA) activation. In contrast to other cell types, the cyclooxygenase/prostaglandin pathway, known to activate the cAMP/PKA cascade, plays little, if any, role in c-fos expression downstream of the IL-1 receptor in keratinocytes. Simultaneous activation of several of the mitogen-activated protein kinase (MAPK) cascades occurred in response to IL-1, but each differentially contributed to c-fos induction by IL-1, with the p38/MAPK being the most crucial of all, the extracellular signal-regulated kinase pathway contributing in an additive manner and the Jun N-terminal kinase pathway playing little, if any, role. We also demonstrate that p38-dependent activation of mitogen- and stress-activated kinase 1 (MSK1), a CREB kinase, is a key step for c-fos gene activation by IL-1. Finally, we identify MSK1 as playing a positive role in the control of cell proliferation of both HaCaT keratinocytes and the A431 human epidermoid carcinoma line.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

CREB:

cAMP response element binding protein

FCS:

fetal calf serum

IL-1:

interleukin-1

MAPK:

mitogen-activated protein kinase

MSK:

mitogen- and stress-activated kinase

PKA:

protein kinase A

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Acknowledgements

This work was supported by INSERM and Association pour la Recherche contre le Cancer (ARC). MS was the recipient of a (DFG) postdoctoral fellowship (Schi 585/2-1). SD is the recipient of a postdoctoral fellowship from the Association pour la Recherche contre le Cancer (ARC, France). MS and MB were supported by a grant from the Innovative Medizinische Forschung (IMF, SC11044), University of Münster, Germany.

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Authors and Affiliations

  1. INSERM U697, Hôpital Saint-Louis, Paris, France

    M Schiller, S Dennler & A Mauviel

  2. Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Münster, Germany

    M Schiller, M Böhm & J M Ehrchen

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  1. M Schiller
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  2. M Böhm
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Correspondence to A Mauviel.

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Schiller, M., Böhm, M., Dennler, S. et al. Mitogen- and stress-activated protein kinase 1 is critical for interleukin-1-induced, CREB-mediated, c-fos gene expression in keratinocytes. Oncogene 25, 4449–4457 (2006). https://doi.org/10.1038/sj.onc.1209479

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