Positive regulation of the skeletal α-actin gene by Fos and Jun in cardiac myocytes

N. H. Bishopric, V. Jayasena, K. A. Webster

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Abstract

Transcription of the skeletal α-actin gene is selectively activated in rat myocardiocytes undergoing hypertrophy both in vivo and in vitro. In most of these models, transient expression of certain proto-oncogene transcription factors precedes hypertrophy and sarcomeric gene induction. Using expression vectors encoding Fos and Jun, the main constituents of transcriptional activator protein AP-1, we analyzed the role of these oncoproteins in mediating the transcriptional induction of skeletal α-actin by adrenergic stimulation. Both c-fos and c-jun were induced early after β-adrenergic stimulation, with peak mRNA levels preceding skeletal α-actin induction by several hours. A second peak of c-jun mRNA coincided with skeletal α-actin induction. Co-transfection assays in cardiac myocytes and P19 teratocarcinoma cells demonstrated that over-expression of c-jun, or c-fos plus c-jun, transactivated the skeletal α-actin promoter by about 5-fold. Comparable activation was not seen for α-myosin heavy chain or cardiac α-actin promoters. Skeletal α-actin promoter sequences between -153 and -36 were required for maximal transactivation by c-fos/c-jun, and purified Fos and Jun were bound specifically within this region. A direct physiological role is suggested for the AP-1 transcription factor complex in regulating skeletal α-actin gene expression and α-actin isoform switching during the onset of signal-mediated cardiac myocyte hypertrophy.

Original languageEnglish (US)
Pages (from-to)25535-25540
Number of pages6
JournalJournal of Biological Chemistry
Volume267
Issue number35
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bishopric, N. H., Jayasena, V., & Webster, K. A. (1992). Positive regulation of the skeletal α-actin gene by Fos and Jun in cardiac myocytes. Journal of Biological Chemistry, 267(35), 25535-25540.