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Induction of activating transcription factor 3 by anoxia is independent of p53 and the hypoxic HIF signalling pathway

Oncogene volume 26, pages 284–289 (2007)Cite this article

Abstract

Solid tumors often have an inadequate blood supply, which results in large regions that are subjected to hypoxic or anoxic stress. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates much of the transcriptional response of cells to hypoxia. Activating transcription factor 3 (ATF3) is another transcription factor that responds to a variety of stresses and is often upregulated in cancer. We investigated the regulation of ATF3 by oxygen deprivation. ATF3 induction occurred most robustly under anoxia, is common, and it is not dependent on presence of HIF-1 or p53, but is sensitive to the inhibition of c-Jun NH2-terminal kinase activation and the antioxidant N-acetylcystein. ATF3 could also be induced by desferrioxamine but not by the mitochondrial poison cyanide or the nonspecific 2-oxoglutarate dioxygenase inhibitor dimethyloxalylglycine. We also show that anoxic ATF3 mRNA is more stable than normoxic mRNA providing a mechanism for this induction. Thus, this study demonstrates that the regulation of ATF3 under anoxia is independent of 2-oxoglutarate dioxygenase, HIF-1 and p53, presumably involving multiple regulatory pathways.

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Acknowledgements

Part of this work was supported by grants to K Ameri from the EU research training network for young scientists (HPRN-CT-2000-0089), to T Hai from NIH (DK59605), and to N Denko from the NCI.

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Author notes

  1. N Denko and A L Harris: These two authors contributed equally as senior authors

Authors and Affiliations

  1. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA

    K Ameri, E M Hammond & N Denko

  2. Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology-Biotechnology, Munich, Germany

    C Culmsee & E Wagner

  3. Department of Hematology/Oncology, University of Leipzig, Germany

    M Raida

  4. Department of Heart and Circulatory Physiology, Center of Physiology and Pathophysiology, Georg-August University of Gottingen, Gottingen, Germany

    D M Katschinski

  5. Institute of Physiology, Cellular Oxygen Physiology, University of Zurich, Zurich,, Switzerland

    R H Wenger

  6. Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    R J Davis

  7. Department of Molecular and Cellular Biochemistry, Center for Molecular Neurobiology, the Ohio State University, Columbus, OH, USA

    T Hai

  8. Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Cancer Research UK, Oxford, UK

    A L Harris

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  1. K Ameri
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  2. E M Hammond
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  3. C Culmsee
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Correspondence to K Ameri.

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Ameri, K., Hammond, E., Culmsee, C. et al. Induction of activating transcription factor 3 by anoxia is independent of p53 and the hypoxic HIF signalling pathway. Oncogene 26, 284–289 (2007). https://doi.org/10.1038/sj.onc.1209781

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  • DOI: https://doi.org/10.1038/sj.onc.1209781

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