Article

Protein Glutathionylation in the Regulation of Peroxiredoxins: A Family of Thiol-Specific Peroxidases That Function As Antioxidants, Molecular Chaperones, and Signal Modulators

School of Biological Sciences and Technology, Chonnam National University, Gwangju, Korea.
Antioxidants & Redox Signaling (Impact Factor: 7.41). 11/2011; 16(6):506-23. DOI: 10.1089/ars.2011.4260
Source: PubMed

ABSTRACT

Reversible protein glutathionylation plays an important role in cellular regulation, signaling transduction, and antioxidant defense. This redox-sensitive mechanism is involved in regulating the functions of peroxiredoxins (Prxs), a family of ubiquitously expressed thiol-specific peroxidase enzymes. Glutathionylation of certain Prxs at their active-site cysteines not only provides reducing equivalents to support their peroxidase activity but also protects Prxs from irreversible hyperoxidation. Typical 2-Cys Prx also functions as a molecular chaperone when it exists as a decamer and/or higher molecular weight complexes. The hyperoxidized sulfinic derivative of 2-Cys Prx is reactivated by sulfiredoxin (Srx). In this review, the roles of glutathionylation in the regulation of Prxs are discussed with respect to their molecular structure and functions as antioxidants, molecular chaperones, and signal modulators. RECENT ADVANCES: Recent findings reveal that glutathionylation regulates the quaternary structure of Prx. Glutathionylation of Prx I at Cys(83) converts the decameric Prx to its dimers with the loss of chaperone activity. The findings that dimer/oligomer structure specific Prx I binding proteins, e.g., phosphatase and tensin homolog (PTEN) and mammalian Ste20-like kinase-1 (MST1), regulate cell cycle and apoptosis, respectively, suggest a possible link between glutathionylation and those signaling pathways.
Knowing how glutathionylation affects the interaction between Prx I and its nearly 20 known interacting proteins, e.g., PTEN and MST1 kinase, would reveal new insights on the physiological functions of Prx.
In vitro studies reveal that Prx oligomerization is linked to its functional changes. However, in vivo dynamics, including the effect by glutathionylation, and its physiological significance remain to be investigated.

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    • "Peroxiredoxins are subject to various post-translational modifications which influence their peroxidase activity or other properties . For instance, phosphorylation of Thr90 in human Prx1 and Thr89 in Prx2 attenuates peroxidase activity and promotes chaperone holdase activity whereas Ser32 phosphorylation of Prx1 is reported to increase peroxidase activity (Chae et al., 2012;Chang et al., 2002;Jang et al., 2006;Qu et al., 2007;Zykova et al., 2010). N-terminal acetylation of human Prx2 was found to influence hyperoxidation sensitivity (Seo et al., 2009). "
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    ABSTRACT: Peroxiredoxins are highly conserved and abundant peroxidases. Although the thioredoxin peroxidase activity of peroxiredoxin (Prx) is important to maintain low levels of endogenous hydrogen peroxide, Prx have also been shown to promote hydrogen peroxide-mediated signalling. Mitogen activated protein kinase (MAPK) signalling pathways mediate cellular responses to a variety of stimuli, including reactive oxygen species (ROS). Here we review the evidence that Prx can act as both sensors and barriers to the activation of MAPK and discuss the underlying mechanisms involved, focusing in particular on the relationship with thioredoxin.
    Preview · Article · Jan 2016 · Moleculer Cells
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    • "Peroxiredoxins are subject to various post-translational modifications which influence their peroxidase activity or other properties . For instance, phosphorylation of Thr90 in human Prx1 and Thr89 in Prx2 attenuates peroxidase activity and promotes chaperone holdase activity whereas Ser32 phosphorylation of Prx1 is reported to increase peroxidase activity (Chae et al., 2012;Chang et al., 2002;Jang et al., 2006;Qu et al., 2007;Zykova et al., 2010). N-terminal acetylation of human Prx2 was found to influence hyperoxidation sensitivity (Seo et al., 2009). "
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    ABSTRACT: The peroxiredoxins (Prxs) constitute a very large and highly conserved family of thiol-based peroxidases that has been discovered only very recently. We consider here these enzymes through the angle of their discovery, and of some features of their molecular and physiological functions, focusing on complex phenotypes of the gene mutations of the 2-Cys Prxs subtype in yeast. As scavengers of the low levels of H2O2 and as H2O2 receptors and transducers, 2-Cys Prxs have been highly instrumental to understand the biological impact of H2O2, and in particular its signaling function. 2-Cys Prxs can also become potent chaperone holdases, and unveiling the in vivo relevance of this function, which is still not established, should further increase our knowledge of the biological impact and toxicity of H2O2. The diverse molecular functions of 2-Cys Prx explain the often-hard task of relating them to peroxiredoxin genes phenotypes, which underscores the pleiotropic physiological role of these enzymes and complex biologic impact of H2O2.
    Preview · Article · Jan 2016 · Moleculer Cells
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    • "Peroxiredoxins are subject to various post-translational modifications which influence their peroxidase activity or other properties . For instance, phosphorylation of Thr90 in human Prx1 and Thr89 in Prx2 attenuates peroxidase activity and promotes chaperone holdase activity whereas Ser32 phosphorylation of Prx1 is reported to increase peroxidase activity (Chae et al., 2012;Chang et al., 2002;Jang et al., 2006;Qu et al., 2007;Zykova et al., 2010). N-terminal acetylation of human Prx2 was found to influence hyperoxidation sensitivity (Seo et al., 2009). "
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    ABSTRACT: Peroxiredoxins are ubiquitous thiol proteins that catalyse the breakdown of peroxides and regulate redox activity in the cell. Kinetic analysis of their reactions is required in order to identify substrate preferences, to understand how molecular structure affects activity and to establish their physiological functions. Various approaches can be taken, including the measurement of rates of individual steps in the reaction pathway by stopped flow or competitive kinetics, classical enzymatic analysis and measurement of peroxidaseactivity. Each methodology has its strengths and they can often give complementary information. However,it is important to understand the experimental conditions of the assay so as to interpret correctly what parameter is being measured. This brief review discusses different kinetic approaches and the information that can be obtained from them.
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