FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage

Young Min Chung, See Hyoung Park, Wen Bin Tsai, Shih Ya Wang, Masa Aki Ikeda, Jonathan S. Berek, David J. Chen, Mickey C T Hu

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

DNA damage as a result of environmental stress is recognized by sensor proteins that trigger repair mechanisms, or, if repair is unsuccessful, initiate apoptosis. Defects in DNA damage-induced apoptosis promote genomic instability and tumourigenesis. The protein ataxia-telangiectasia mutated (ATM) is activated by DNA double-strand breaks and regulates apoptosis via p53. Here we show that FOXO3 interacts with the ATMĝ€"Chk2ĝ€"p53 complex, augments phosphorylation of the complex and induces the formation of nuclear foci in cells on DNA damage. FOXO3 is essential for DNA damage-induced apoptosis and conversely FOXO3 requires ATM, Chk2 and phosphorylated p53 isoforms to trigger apoptosis as a result of DNA damage. Under these conditions FOXO3 may also have a role in regulating chromatin retention of phosphorylated p53. These results suggest an essential link between FOXO3 and the ATMg53-mediated apoptotic programme following DNA damage.

Original languageEnglish (US)
Article number1000
JournalNature Communications
Volume3
DOIs
StatePublished - 2012

Fingerprint

ataxia
Ataxia Telangiectasia
DNA Damage
apoptosis
deoxyribonucleic acid
damage
Apoptosis
DNA
Ataxia Telangiectasia Mutated Proteins
Repair
actuators
Double-Stranded DNA Breaks
proteins
Genomic Instability
phosphorylation
chromatin
Phosphorylation
Chromatin
Protein Isoforms
strands

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Chung, Y. M., Park, S. H., Tsai, W. B., Wang, S. Y., Ikeda, M. A., Berek, J. S., ... Hu, M. C. T. (2012). FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. Nature Communications, 3, [1000]. https://doi.org/10.1038/ncomms2008

FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. / Chung, Young Min; Park, See Hyoung; Tsai, Wen Bin; Wang, Shih Ya; Ikeda, Masa Aki; Berek, Jonathan S.; Chen, David J.; Hu, Mickey C T.

In: Nature Communications, Vol. 3, 1000, 2012.

Research output: Contribution to journalArticle

Chung, YM, Park, SH, Tsai, WB, Wang, SY, Ikeda, MA, Berek, JS, Chen, DJ & Hu, MCT 2012, 'FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage', Nature Communications, vol. 3, 1000. https://doi.org/10.1038/ncomms2008
Chung, Young Min ; Park, See Hyoung ; Tsai, Wen Bin ; Wang, Shih Ya ; Ikeda, Masa Aki ; Berek, Jonathan S. ; Chen, David J. ; Hu, Mickey C T. / FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. In: Nature Communications. 2012 ; Vol. 3.
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