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Growth factor stimulation induces cell survival by c-Jun. ATF2-dependent activation of Bcl-XL

Ahmad Salameh1, Federico Galvagni, Francesca Anselmi

  • 1Dipartimento di Biologia Molecolare, Universita' di Siena, 53100 Siena, Italy.

The Journal of Biological Chemistry
|May 29, 2010
PubMed

Insights

Growth factors promote cell survival by increasing c-Jun expression, which binds ATF2 to activate the anti-apoptotic Bcl-X(L) protein. This c-Jun.ATF2 dimer mechanism explains cell survival pathways.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Growth factor stimulation promotes endothelial cell survival via c-Jun.
  • The precise mechanism of c-Jun's anti-apoptotic function remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which c-Jun mediates anti-apoptotic activity.
  • To identify the downstream targets and signaling pathways involved in growth factor-induced cell survival.

Main Methods:

  • Quantitative real-time PCR to measure gene expression.
  • Western blotting to detect protein levels and complex formation.
  • Site-directed mutagenesis to analyze promoter activity.
  • Chromatin immunoprecipitation (ChIP) to assess protein-DNA binding.
  • siRNA-mediated gene silencing to knock down c-Jun and ATF2.

Main Results:

  • Growth factor treatment increased c-Jun expression, forming a complex with ATF2.
  • The c-Jun.ATF2 complex was found to activate the expression of the anti-apoptotic protein Bcl-X(L).
  • Two AP-1 binding sites in the Bcl-X promoter were identified as crucial for transcriptional activation by c-Jun.ATF2.
  • ChIP assays confirmed that the c-Jun.ATF2 dimer binds to these sites upon growth factor stimulation.
  • Silencing of c-Jun or ATF2 abolished the activation of the Bcl-X promoter.

Conclusions:

  • Growth factor signaling converges on the formation of an active c-Jun.ATF2 dimer.
  • This dimer induces Bcl-X(L) expression, mediating a pro-survival response in endothelial cells and fibroblasts.
  • The study reveals a novel mechanism for c-Jun-dependent cell survival involving Bcl-X(L) regulation.

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