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Structural basis for DNA recognition by FOXO proteins

Tomas Obsil1, Veronika Obsilova

  • 1Department of Physical and Macromolecular Chemistry, Faculty of Science, Charles University, 128 43 Prague, Czech Republic. obsil@natur.cuni.cz

Biochimica Et Biophysica Acta
|December 15, 2010
PubMed

Insights

FOXO transcription factors regulate key cellular processes. Recent structural studies reveal how FOXO proteins bind DNA and how modifications like phosphorylation control this crucial DNA-binding activity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • FOXO (forkhead box) transcription factors are crucial regulators of cellular functions including metabolism, survival, proliferation, DNA repair, and stress resistance.
  • Their activity is modulated by post-translational modifications such as phosphorylation, acetylation, and ubiquitination.

Purpose of the Study:

  • To review recent structural insights into FOXO protein-DNA interactions.
  • To elucidate the mechanisms of DNA recognition by FOXO proteins.
  • To summarize the role of post-translational modifications in regulating FOXO DNA-binding properties.

Main Methods:

  • Structural biology techniques (e.g., X-ray crystallography) to determine three-dimensional structures of FOXO forkhead domains bound to DNA.
  • Bioinformatic analysis to understand DNA recognition mechanisms.
  • Literature review of studies on FOXO post-translational modifications and their impact on DNA binding.

Main Results:

  • Recent structural data provide a detailed understanding of the atomic basis for FOXO protein recognition of specific DNA sequences.
  • Post-translational modifications directly influence the conformation and DNA-binding affinity of FOXO proteins.
  • The interplay between structural features and modifications dictates FOXO transcriptional output.

Conclusions:

  • Structural characterization of FOXO proteins bound to DNA is key to understanding their regulatory mechanisms.
  • Post-translational modifications play a critical role in fine-tuning FOXO DNA-binding activity and downstream functions.
  • This knowledge is vital for understanding the PI3K-AKT-FOXO pathway in cancer and aging.

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