FEBS Letters
Volume 582, Issue 7 , Pages 1025-1031, 2 April 2008

A role for p38α mitogen-activated protein kinase in embryonic cardiac differentiation

Edited by Lukas Hüber

  • Francisco Hernández-Torres

      Affiliations

    • Departamento de Biología Experimental, Facultad de Ciencias Experimentales, Universidad de Jaén, Paraje de las Lagunillas, s/n, 23071 Jaén, Spain
    • ,
  • Sergio Martínez-Fernández

      Affiliations

    • Departamento de Biología Experimental, Facultad de Ciencias Experimentales, Universidad de Jaén, Paraje de las Lagunillas, s/n, 23071 Jaén, Spain
    • ,
  • Susana Zuluaga

      Affiliations

    • Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, UCM, Ciudad Universitaria, 28040 Madrid, Spain
    • ,
  • Ángel Nebreda

      Affiliations

    • CNIO (Spanish National Cancer Center), Madrid, Spain
    • ,
  • Almudena Porras

      Affiliations

    • Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, UCM, Ciudad Universitaria, 28040 Madrid, Spain
    • ,
  • Amelia E. Aránega

      Affiliations

    • Departamento de Biología Experimental, Facultad de Ciencias Experimentales, Universidad de Jaén, Paraje de las Lagunillas, s/n, 23071 Jaén, Spain
    • Corresponding Author InformationCorresponding authors. Fax: +34 953 211875 (F. Navarro), +34 953 211875 (A.E. Aránega).
    • ,
  • Francisco Navarro

      Affiliations

    • Departamento de Biología Experimental, Facultad de Ciencias Experimentales, Universidad de Jaén, Paraje de las Lagunillas, s/n, 23071 Jaén, Spain
    • Corresponding Author InformationCorresponding authors. Fax: +34 953 211875 (F. Navarro), +34 953 211875 (A.E. Aránega).

Received 17 December 2007; received in revised form 22 January 2008; accepted 21 February 2008. published online 29 February 2008.

Abstract 

Cardiac differentiation involves cross-regulation of several transcription factors, such as Mef2C, regulated by p38α MAP kinase. We analysed the role of p38α in cardiac differentiation. Either the absence or inhibition of p38α impairs MEF2C nuclear localization in cardiomyocytes, colocalising with vimentin at the perinuclear region. As a consequence, expression of the Mef2C targets, ANF and myocardin, is drastically downregulated. In contrast, Mlc2v and crt are mainly unaltered, probably by the strong Mef2B upregulation, conpensating for the impaired Mef2C transactivity. In addition, p38α deficiency leads to a decrease in the phosphorylated Mlc2v fraction and α-actinin accumulation causing sarcomere disorganisation. We propose a critical role for p38α in early stages of cardiac differentiation by modulation of Mef2C localisation and sarcomeric assembly.

Keywords: Cardiomyocyte, Transcription factor, Mef2C, MAP kinases, Cardiac differentiation

 

PII: S0014-5793(08)00165-8

doi:10.1016/j.febslet.2008.02.050

FEBS Letters
Volume 582, Issue 7 , Pages 1025-1031, 2 April 2008

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