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Temporal coordination of the transcription factor response to H2O2 stress

Author

Listed:
  • Elizabeth Jose

    (University of Arizona)

  • Woody March-Steinman

    (University of Arizona)

  • Bryce A. Wilson

    (University of Arizona)

  • Lisa Shanks

    (University of Arizona)

  • Chance Parkinson

    (University of Arizona)

  • Isabel Alvarado-Cruz

    (University of Arizona College of Medicine)

  • Joann B. Sweasy

    (University of Arizona College of Medicine
    University of Arizona Cancer Center
    University of Nebraska Medical Center)

  • Andrew L. Paek

    (University of Arizona
    University of Arizona
    University of Arizona Cancer Center)

Abstract

Oxidative stress from excess H2O2 activates transcription factors that restore redox balance and repair oxidative damage. Although many transcription factors are activated by H2O2, it is unclear whether they are activated at the same H2O2 concentration, or time. Dose-dependent activation is likely as oxidative stress is not a singular state and exhibits dose-dependent outcomes including cell-cycle arrest and cell death. Here, we show that transcription factor activation is both dose-dependent and coordinated over time. Low levels of H2O2 activate p53, NRF2 and JUN. Yet under high H2O2, these transcription factors are repressed, and FOXO1, NF-κB, and NFAT1 are activated. Time-lapse imaging revealed that the order in which these two groups of transcription factors are activated depends on whether H2O2 is administered acutely by bolus addition, or continuously through the glucose oxidase enzyme. Finally, we provide evidence that 2-Cys peroxiredoxins control which group of transcription factors are activated.

Suggested Citation

  • Elizabeth Jose & Woody March-Steinman & Bryce A. Wilson & Lisa Shanks & Chance Parkinson & Isabel Alvarado-Cruz & Joann B. Sweasy & Andrew L. Paek, 2024. "Temporal coordination of the transcription factor response to H2O2 stress," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47837-w
    DOI: 10.1038/s41467-024-47837-w
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    References listed on IDEAS

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    1. Philipp Niethammer & Clemens Grabher & A. Thomas Look & Timothy J. Mitchison, 2009. "A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish," Nature, Nature, vol. 459(7249), pages 996-999, June.
    2. Deepti Talwar & Joris Messens & Tobias P. Dick, 2020. "A role for annexin A2 in scaffolding the peroxiredoxin 2–STAT3 redox relay complex," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    3. Keito Okazaki & Hayato Anzawa & Zun Liu & Nao Ota & Hiroshi Kitamura & Yoshiaki Onodera & Md. Morshedul Alam & Daisuke Matsumaru & Takuma Suzuki & Fumiki Katsuoka & Shu Tadaka & Ikuko Motoike & Mika W, 2020. "Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
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