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

Authors

Dmitri E. Fomenko, University of Nebraska-LincolnFollow
Ahmet Koc, University of Nebraska-Lincoln
Natalia Agisheva, University of Nebraska-Lincoln
Michael Jacobsen, University of Nebraska-Lincoln
Alaattin Kaya, University of Nebraska-Lincoln
Mikalai Malinouski, University of Nebraska-Lincoln
Julian C. Rutherford, University of Utah
Kam-Leung Siu, University of Hong Kong
Dong-Yan Jin, University of Hong Kong
Dennis R. Winge, University of Utah
Vadim N. Gladyshev, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

2011

Comments

Published in PNAS, February 15, 2011, vol. 108, no. 7, 2729–2734. Used by Permission.

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 H₂O₂ 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.