FOXO3a Is Activated in Response to Hypoxic Stress and Inhibits HIF1-Induced Apoptosis via Regulation of CITED2

We report a role for FOXO3a under conditions of hypoxic stress

Walbert J. Bakker; Isaac S. Harris; Tak W. Mak

2008

Scholarcy highlights

  • The FOXO subfamily of Forkhead transcription factors plays an evolutionarily conserved role in cellular adaptation to stress stimuli
  • Foxo3 Activity Is Induced by Hypoxia in an Hif1-Dependent Manner To explore a potential role for FOXO proteins under hypoxic stress, mouse embryonic fibroblasts and NIH 3T3 fibroblasts were cultured under hypoxia for 24 or 48 hr, respectively
  • To test whether Foxo3 is regulated at the transcriptional level, MEF and NIH 3T3 cells were cultured under hypoxia for 8 or 24 hr, respectively, and Foxo3 mRNA levels were determined by quantitative PCR
  • Foxo3 transcripts were increased in response to hypoxia in both MEF and NIH 3T3 cells
  • To determine whether Foxo3 transcription was regulated by Hif1, WT and Hif1aÀ/À MEFs were cultured for 24 hr under normal conditions and under hypoxia, after which transcript levels of Foxo1, Foxo3, 942 Molecular Cell 28, 941–953, December 28, 2007 a2007 Elsevier Inc
  • They can be activated by a wide range of stress stimuli, in response to which they can regulate a broad variety of cellular mechanisms
  • By fine-tuning HIF1 activity, FOXO3a plays an important role in the survival response of normal and cancer cells in response to hypoxic stress

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