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Direct control of caveolin-1 expression by FOXO transcription factors

A Pieter J van den Heuvel1, Almut Schulze, Boudewijn M T Burgering

  • 1Laboratory of Physiological Chemistry and Centre for Biomedical Genetics, University Medical Center Utrecht, Stratenum, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.

The Biochemical Journal
|October 2, 2004
PubMed

Insights

Forkhead box O (FOXO) transcription factors directly regulate caveolin-1 expression. This FOXO-mediated transcriptional activation of caveolin-1 influences cellular signaling pathways.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Gene Regulation

Background:

  • Protein kinase B inactivates FOXO transcription factors through phosphorylation.
  • Active FOXO factors bind DNA to regulate gene expression.
  • Identifying FOXO target genes is crucial for understanding its cellular functions.

Purpose of the Study:

  • To investigate the regulatory relationship between FOXO transcription factors and caveolin-1.
  • To elucidate the mechanism by which FOXO influences caveolin-1 expression.
  • To explore the role of caveolin-1 in FOXO-mediated signaling attenuation.

Main Methods:

  • DNA microarray analysis to identify potential FOXO gene targets.
  • Quantitative analysis of mRNA and protein levels for caveolin-1.
  • Chromatin immunoprecipitation assays to assess FOXO binding to the caveolin-1 promoter.
  • Functional studies using dominant-negative FOXO to inhibit endogenous regulation.

Main Results:

  • FOXO factors directly activate transcription of the caveolin-1 gene.
  • Caveolin-1 expression (mRNA and protein) increases upon FOXO induction or overexpression.
  • FOXO directly binds to the caveolin-1 promoter, confirmed by chromatin immunoprecipitation.
  • FOXO-mediated attenuation of epidermal growth factor (EGF)-induced signaling involves caveolin-1.

Conclusions:

  • Caveolin-1 is a direct transcriptional target of FOXO factors.
  • FOXO regulates cellular signaling pathways, including EGF signaling, partly through caveolin-1.
  • This study reveals a novel mechanism for FOXO's cellular functions via caveolin-1 transcriptional activation.

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