Temporal coordination of the transcription factor response to H2O2 stress

Elizabeth Jose, Woody March-Steinman, Bryce A. Wilson, Lisa Shanks, Chance Parkinson, Isabel Alvarado-Cruz, Joann B. Sweasy & Andrew L. Paek

In a recent study by the Paek lab on hydrogen peroxide (H2O2) stress, Elizabeth Jose and colleagues discovered a dose-dependent switch in which transcription factors are activated by H2O2. At low H2O2, 'Group 1' proteins (p53, NRF2 and JUN) are activated, while 'Group 2' proteins (FOXO1, NF-KB, NFAT) remain inactive. However, at higher concentrations, Group 2 proteins are activated while activation of Group 1 proteins is delayed until Group 2 proteins switch off. Prolonged activation of Group 2 is linked to cell death, underscoring the concept that oxidative stress can be categorized as eustress (mild and beneficial) or distress (severe, causing damage and disease). Their findings reveal the shift between oxidative eustress to distress is not gradual but dramatic, resembling a phase transition.

This paper was published in Nature Communications; read the complete study here.