Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

DNA damage

The road of death

Nature Reviews Molecular Cell Biology volume 7, page 878 (2006)Cite this article

Access through your institution
Buy or subscribe

Given that FOXO transcription factors control a number of cell-death genes, Tindall and co-workers investigated a possible connection between CDK2 and the activity of FOXO proteins. They found that endogenous CDK2 phosphorylates FOXO1 at residue Ser249, and to a lesser degree residue Ser298, in vitro. This effect was abolished by a CDK inhibitor. The authors developed a phosphorylation-specific antibody and provided in vivo evidence for the CDK2-dependent phosphorylation of FOXO1. The antibody recognized wild-type FOXO1, but not a Ser249 to Ala249 (S249A) mutant of FOXO1. Small-interfering RNA (siRNA)-mediated silencing of CDK2 led to a decrease in FOXO1 phosphorylation, whereas FOXO1 phosphorylation was increased in cells that had been transfected with a constitutively active CDK2 mutant.

The transcriptional activity of FOXO1 was decreased in the presence of ectopically expressed CDK2 and its regulator cyclin E. By contrast, its transcriptional activity was increased by co-transfection of the tumour suppressor phosphatase and tensin homologue (PTEN), which promotes a decrease in FOXO1 phosphorylation. The increased transcriptional activity of FOXO1 was abolished in the presence of wild-type CDK2, but not by a kinase-inactive CDK2 mutant. Also, the inhibitory effect of CDK2 was diminished in a FOXO1 (Ser249, Ser298) double mutant. Together, these data indicate that the transcriptional activity of FOXO1 is repressed primarily by the CDK2-mediated phosphorylation of Ser249.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

ORIGINAL RESEARCH PAPER

  1. Huang, H. et al. CDK2-dependent phosphorylation of FOXO1 as an apoptotic response to DNA damage. Science 314, 294–297 (2006)

    Article  CAS  Google Scholar 

FURTHER READING

  1. Bartek, J. et al. Checking on DNA damage in S phase. Nature Rev. Mol. Cell Biol. 5, 792–804 (2006)

    Article  Google Scholar 

Download references

Authors
  1. Arianne Heinrichs
    View author publications

    Search author on:PubMed Google Scholar

Related links

Related links

WEB SITE

Donald Tindall's laboratory

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heinrichs, A. The road of death. Nat Rev Mol Cell Biol 7, 878 (2006). https://doi.org/10.1038/nrm2073

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nrm2073

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing