Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide

Dmitri E. Fomenko, Ahmet Koc, Natalia Agisheva, Michael Jacobsen, Alaattin Kaya, Mikalai Malinouski, Julian C. Rutherford, Kam Leung Siu, Dong Yan Jin, Dennis R. Winge, Vadim N. Gladyshev

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Abstract

Hydrogen peroxide is thought to regulate cellular processes by direct oxidation of numerous cellular proteins, whereas antioxidants, most notably thiol peroxidases, are thought to reduce peroxides and inhibit H 2O2 response. However, thiol peroxidases have also been implicated in activation of transcription factors and signaling. It remains unclear if these enzymes stimulate or inhibit redox regulation and whether this regulation is widespread or limited to a few cellular components. Herein, we found that Saccharomyces cerevisiae cells lacking all eight thiol peroxidases were viable and withstood redox stresses. They transcriptionally responded to various redox treatments, but were unable to activate and repress gene expression in response to H2O2. Further studies involving redox transcription factors suggested that thiol peroxidases are major regulators of global gene expression in response to H2O2. The data suggest that thiol peroxidases sense and transfer oxidative signals to the signaling proteins and regulate transcription, whereas a direct interaction between H2O2 and other cellular proteins plays a secondary role.

Original languageEnglish (US)
Pages (from-to)2729-2734
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number7
DOIs
StatePublished - Feb 15 2011

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Fomenko, D. E., Koc, A., Agisheva, N., Jacobsen, M., Kaya, A., Malinouski, M., Rutherford, J. C., Siu, K. L., Jin, D. Y., Winge, D. R., & Gladyshev, V. N. (2011). Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 2729-2734. https://doi.org/10.1073/pnas.1010721108