Abstract
The yeast Saccharomyces cerevisiae is a model organism for biochemical and genetic studies, and several very important discoveries of fundamental biological processes have been conducted using this yeast as an experimental organism. An emerging concept, which is validated by several works using this organism, relies on the biological importance of oxidant species, specially the hydroperoxides. These molecules were formed during aerobic biological process and control several intracellular mechanisms such as a range of signaling pathways, cell cycle, programmed cell death, circadian rhythm, aging, and lifespan extension. Thereby, cellular homeostasis depends on a refined control of hydroperoxides levels and low-molecular-weight molecules in combination with antioxidant enzymes playing a role in this equilibrium. This proposal is focused on the S. cerevisiae peroxiredoxins and their role in peroxide decomposition, signal transduction, circadian clocks, and aging as model enzymes for the study and comprehension of these biological processes in living organisms, including humans.
Keywords
- thiol-specific antioxidant protein
- functional transitions
- peroxidase
- chaperone
- overoxidation
1. Introduction
The use of
The first Prx described was a cytosolic enzyme identified in
Besides the widespread cellular distribution and abundance, Prx stands out due to their highly efficient ability to decompose a wide variety of hydroperoxides (H2O2, nitrite peroxide, lipid peroxides, among others), with second order rates reaching ~106–108 M−1 s−1) [18–21]. These characteristics place the Prx as one of the main modulators of hydroperoxides levels and, consequently, of the cellular processes mediated by them. The Prx enzymes are able to decompose hydroperoxides without any prosthetic group, but using only a highly reactive cysteine residue named peroxidatic cysteine (CP) [5, 22]. All the Prxs described to date present a conserved motif containing the CP (PXXXT/SXXCP), which is oxidized to cysteine sulfenic acid (CP-SOH) after hydroperoxide reduction [10]. This enzyme family is very heterogeneous, and different classifications have been proposed; the most currently used one subdivides these proteins in three large subclasses,1-Cys Prx, typical 2-Cys Prx, and atypical 2-Cys Prx, based in the number of cysteines involved in catalytic cycle and structural aspects ( Figure 1 ). The 1-Cys Prxs are homodimeric proteins that present only one cysteine residue, the CP, involved in hydroperoxide catalysis. 2-Cys Prxs may be monomeric (in the case of some atypical 2-Cys Prx) or homodimeric proteins and present a second cysteine residue, named resolving cysteine (CR), which condenses with CP forming a disulfide bond as final product during the catalytic cycle. In typical 2-Cys Prx, the disulfide is intermolecular (e.g., between different monomers), while in atypical 2-Cys Prx, the disulfide is intramolecular (in the same monomer) [23].
Among the different Prx subclasses, the typical 2-Cys Prxs are the best studied, and, from this point on, our focus will be on this Prx subclass. After oxidation, the disulfide bond of the typical 2-Cys Prx is frequently reduced by the low-molecular-weight (~11 kDa) enzyme thioredoxin (Trx). The oxidized Trx is reduced by thioredoxin reductase (TrxR), which uses electrons from nicotinamide adenine dinucleotide phosphate (NADPH)
Despite that the basic functional unit of the typical 2-Cys Prx is represented by a α(2) homodimer, studies using the Tsa1 and Tsa2 isoforms from
The high reactivity of Prx over hydroperoxides is related to the maintenance of CP in thiolate form (CP-S−), suitable for catalysis as a consequence of the microenvironment of the active site. The CP thiolate is stabilized by polar interactions with a threonine (or a serine, in some cases) and an arginine residue ( Figure 3C ). These three residues (Thr, CP, and Arg) are named catalytic triad and are widely conserved among all Prxs described to date [10]. During catalysis, a guanidine group of the Arg residue is able to perform a hydrogen bond with the proximal oxygen (O) of the hydroperoxide, allowing the nucleophilic attack of the CP over the hydroperoxide [24]. The Oγ from Thr, in turn, would act as an acceptor of the hydrogen bond with the distal O from hydroperoxide, aiding the positioning of the molecule in a productive way to catalysis [24].
Typical 2-Cys Prxs, such as
2. Redox cycle and structural transitions
During the redox cycle, some typical 2-Cys Prxs are able to transit between different oligomeric species: α2(5) decamers (reduced enzyme) and α2 dimers (disulfide oxidized protein). Aiming to understand the details of the catalytic cycle and structural transitions, we have determined the crystallographic structure of Tsa1 [21]. In fact, the analysis of the structure revealed an interaction of the Thr from the active site motif, at the dimer-dimer interface of the decamer. Recently, using different methodological approaches as site-directed mutagenesis, biochemical approaches, size exclusion chromatography, and structural analysis, we have demonstrated that a slight difference in the PXXXT(S)XXCP is involved in decamers to dimers transitions [10]. While Tsa1 possess a Thr residue embedded in the conserved motif, in Tsa2, the Thr is naturally substituted by a Ser ( Figure 4 ). In fact, the Tsa1 enzyme, containing Thr residue, transits between dimers (oxidized form) and decamers (reduced enzyme), but the Ser-containing enzyme Tsa2 is not able to dissociate in dimers. Indeed, the rearrangements as consequence of the redox states in the Tsa1 may cause hysteric hindrance of the Thr Oγ with the Tyr aromatic ring of the adjacent monomer, causing the decamer dissociation. Since Tsa2 presents a Ser residue, the hysteric clash probably is avoided. These characteristics may indicate an additional regulation of Prx quaternary structure, which may have implications in biological processes.
3. Prx overoxidation: structural and functional implications
During the typical 2-Cys Prx catalytic cycle under high levels of hydroperoxides, before disulfide formation, CP-SOH can be attacked by another hydroperoxide molecule and becomes overoxidized to cysteine sulfinic acid (CP-SO2H) or sulfonic acid (CP-SO3H). The CP overoxidation is related to spectacular functional and structural switch in typical 2-Cys Prx. As mentioned before, when the typical 2-Cys Prx are in reduced state (CP-S−), these proteins are decamers, but when are oxidized in disulfide, they can be dimers and/or decamers and are able to act as peroxidases (
Figure 5A
and
B
) [9, 11]. However, when the CP is overoxidized, these enzymes are able to promote an intense oligomerization to form high-molecular-weight (HMW) spherical complexes (
Figure 5C
), with the concomitant inactivation of the peroxidase activity. The HMW complexes formation was first reported in
A very important point relies on the fact that the Prx overoxidized species cannot be reduced by the Trx system, but some studies revealed that overoxidized typical 2-Cys Prx species could be regenerated to the reduced form
The sensitive enzymes are present in eukaryotes and in some cyanobacteria, and the robust 2-Cys Prxs are exclusive to prokaryotes [34, 35]. The structural analyses of sensitive versus robust 2-Cys Prx revealed the presence of two motifs in the sensitive 2-Cys Prx. One is an insertion with conserved Gly-Gly-Leu-Gly, denominated GGLG motif (
Figure 6A
), and the other is an additional α-helix in C-terminal extension with a conserved Tyr-Phe sequence, the YF motif, both involved in CP overoxidation susceptibility.
Figure 6
shows the comparison of
4. Typical 2-Cys Prx roles in redox signal transduction pathways
Increasing evidence shows the involvement of the typical 2-Cys Prx with the redox signal transduction pathways. Several antioxidant coding genes are activated by the transcriptional regulator activator protein 1 (AP1) which is considered as the major transcriptional activator of the antioxidant proteins in eukaryotes. It has been shown that the translocation of the homologue factor in budding yeast (YAP1) from cytosol to the nucleus may be controlled by 2-Cys Prx indirectly by the modulation of the cytosolic hydroperoxide levels [36]. In mammals, the PrxII is able to perform a physical interaction with the transcription factor STAT 3 (signal transducer and activator of transcription 3), which is able to activate the transcription of several genes involved in cell growth and apoptosis [37]. The authors demonstrated that PrxII can form mixed disulfides through CP and cysteine residues of the DNA binding and trans-activating domains from STAT3, attenuating its transcriptional activity. Although the direct interaction of the typical 2-Cys Prx with target proteins is still an emerging area, this work reveals that the Prx may be an ultrasensitive hydroperoxide sensor that can form transient disulfides with unknown target proteins, which may have implications in biological processes. Additionally, the mammal PrxI can bind to several proteins including the tumor suppressor phosphatase and tensin homolog (PTEN), protecting it against suppression of its lipid phosphatase activity, which occurs under oxidative stress. On the other hand, PTEN deficiency causes decrease of PrxI, PrxII, PrxV, and PrxVI, suggesting that the Prxs and PTEN act together to maintain cellular antioxidant levels and suppress cancer-promoting pathways, such as the PI3K-Akt pathway [38].
Despite the importance of the physical interaction between typical 2-Cys Prx and biological targets, the indirect role in the regulation of the cell-signaling redox pathways is dependent of an intricate balance between peroxiredoxin, thioredoxin, and sulfiredoxin levels and their redox state. As an example, in yeast, the number of Tsa1 molecules per cell is estimated in 378,000 in aerobic conditions (log phase, SD medium), while its reductants represented by Trx and Srx molecules are much lower (~13,000 and 538 molecules/cell, respectively) [16]. In the case of Trx enzymes, additionally to the Prx reduction, these enzymes are involved in several biological processes as deoxyribonucleotide synthesis, repair of oxidatively damaged proteins, protein folding, sulfur metabolism, and activation of transcription factors among others [16]. The importance of Tsa1 reduction by Trx in redox signaling promoted by hydrogen peroxide may be significant in the cells since it produces oxidized Trx, and many signal transduction pathways are only activated by the reduced Trx enzyme [1, 39]. Because the oxidation of Trx by hydroperoxidesis is negligible, Prxs may act as a catalyst of this reaction in the cells [21].
The typical 2-Cys Prx inactivation by the CP overoxidation combined with the low rates of the reduction of the CP-SO2H by sulfiredoxin (~2 M−1 s−1) [32] is able to enhance levels of the reduced Trx to participate of other biological processes. In fact, it has been shown that the CP overoxidation of the typical 2-Cys Prx from
Finally, the direct modulation of peroxides levels is an important role of the 2-Cys Prx enzymes in cell growth. It has been shown that PrxI and PrxII can eliminate the intracellular hydrogen peroxide generated by the receptors stimulation. Overexpression of PrxI and PrxII in culture cells dramatically reduces the intracellular hydrogen peroxide levels generated in response to platelet-derived growth factor (PDGF), epidermal growth factor (EGF), tirotropin (TSH), and TNF-related apoptosis inducing ligands (TRAIL). Furthermore, it has been shown that the expression of these proteins also led to a block of NF-κβ activity, which is induced by the extracellular addition of H2O2 or tumor necrosis factor α (TNF-α) [44]. It has also been shown that PrxII regulates different MAP kinases. Under stimulation of TNF, in which the activity of PrxII was blocked or partially abolished (knockout and RNAi), the activity of JNK and P38 MAP kinase was increased [45]. Due to the involvement of PrxI and PrxII in cell growth events, several studies have demonstrated that these isoforms have elevated levels in distinct types of cancers in different organs and tissues such as esophagus, pancreas, thyroid, lung, and breast [44–46]. The high expression of PrxI/PrxII is also associated to a more aggressive phenotype of cancer cells resistant to chemotherapy and radiotherapy [44–46].
Some authors argued that the typical 2-Cys Prx enzymes maintain hydrogen peroxide in appropriate levels to cell growth but not to apoptosis. However, Liu et al. [47] showed that the neoplastic cells of acute myeloid leukemia treated with an inhibitor of the PrxI and PrxII peroxidase activity demonstrated that the accumulation of intracellular H2O2 is related to the activation of the ERK1 and ERK2 (extracellular signal regulatory kinases). The kinases activation leads to an increase in the expression of the CCAAT-enhancer-binding proteins β (C/EBPβ). This condition resulted in cell differentiation and consequent tumor regression [47, 48], showing additional complexity of the neoplastic processes with the involvement of the Prx. Since there is a notable resemblance between human and yeasts typical 2-Cys Prx as also other proteins of these pathways, yeasts may be used to explore these mechanisms.
5. Prx structural switch and circadian rhythm
The circadian rhythm is a fundamental process considered to be a feature of almost all living cells. The organisms are able to exhibit cycles in their metabolism, physiology, and behavior, even when isolated from external stimuli, maintaining a 24-h period [49]. However, the molecular mechanisms which drive the circadian rhythm are not simple to elucidate, since the already identified clock genes and proteins are not very conserved across phylogenetic kingdoms [49–53]. A common model for molecular mechanism has been described for all organisms which had their circadian rhythm investigated, named transcription-translation feedback loop (TTFL) [49]. However, the TTFL components are not shared between organisms, suggesting independent evolutionary processes. Additionally, it was showed that nontranscriptional mechanisms are sufficient to sustain circadian timekeeping in the eukaryotic lineage, although they normally function in conjunction with transcriptional components [51].
Recently, it has been demonstrated that in human erythrocytes, a cell type without transcriptional activity, the PrxI and PrxII exhibit an approximate 24-h rhythm according to the CP overoxidation. This characteristic is shared with several organisms, including
Yeast Tsa1 and Tsa2 isoforms exhibit relationship with the shorter period yeast respiratory oscillations, a cell-autonomous, temperature-compensated rhythm in oxygen consumption that synchronizes spontaneously when cells are grown at high density in aerobic, nutrient-limited, continuous culture [52]. Additionally, the yeast respiratory oscillation cycle shares key features with the clock in mammalian cells, which may contribute to the elucidation about the origins of biological timekeeping [52].
Finally, it has been determined that the deregulation of the circadian rhythm is related to aging and genetic diseases [57]. Curiously, it has also been demonstrated that aging is related to the accumulation of the 2-Cys Prx overoxidized species in mammals [58]. Recently, a study involving the overoxidation of Tsa1 revealed that the chaperone activity detected in overoxidized species may be attributed to the association of this protein with the heat shock proteins Hsp70/Hsp104, revealing a pathway where the hydrogen peroxide is directly related to the aging process [12]. The authors also showed that the disaggregation process of the protein is dependent of Srx. Another study demonstrated that the presence of a mutant allele of Tsa1 resulted in accelerated aging in yeast [59]. One of the reasons for the involvement of these enzymes in the senescence process resides in the increase of the level of CP overoxidation in Prx over time, even in the absence of oxidative stress [6]. In fact, this process also involves the caloric restriction, a well-known intervention that extends life span [60]. The caloric restriction elevates the level of Srx, which is responsible to reduce the hyperoxidized Tsa1, the inhibition of Tsa1 causes a profound genome instability, like chromosomal rearrangements and recombination, therefore increasing aging process [6, 61].
Another situation in which Prxs are involved is in the telomere length homeostasis [62]. The telomere dysfunction causes cellular senescence due to DNA damage [63]. The yeast mutant with
6. Methodologies to detect different redox species of the typical 2-Cys Prx
Several methodologies such as transmission electron microscopy (TEM), cryo-electron microscopy (Cryo-EM), size exclusion chromatography (SEC), mass spectrometry (MS), two-dimensional gel electrophoresis (2DGE), nonreducing SDS PAGE, and immunoblotting can be used to explore directly or indirectly the redox state of typical 2-Cys Prx [11, 66, 67]. However, for some experimental procedures, high-cost equipment and/or complex experimental procedures are necessary. Among these techniques, the nonreducing SDS PAGE, immunoblotting, and SEC are very good and cost-effective procedures, since no expensive equipment or complicated protocols are required. In this topic, these techniques and some experimental procedures will be discussed.
To access the formation of HMW complexes of purified 2-Cys Prx samples, the size exclusion chromatography (SEC) is the best choice. This methodology was used in the pioneer work performed by Jang and coworkers [11] using Tsa1 and Tsa2. In our lab, we performed a similar assay, using Tsa1, Trx system, and high concentration of cumene hydroperoxide (CHP) to promote the HMW complexes formation. Using SEC methodology, it is possible to separate several molecular species with mass range from ~45 kDa, correspondent to a dimer, followed by a ~200-kDa peak representing the decameric species, several oligomeric intermediates, and a prominent specie with more than 1000 kDa ( Figure 8 ). These results are in accordance with structural analyses performed by transmission electron microscopy (TEM) by Jang and co-workers [11], using negative stain. These authors analyzed different fractions separated by SEC, and their results revealed three distinct oligomeric configurations: large spherical shaped particles, heterogeneous spherical particles, and ring-shaped structures, as represented in Figure 8 . Currently, the cryo-electron microscopy development has provided pronounced advances to resolve complex protein structures in high resolution, such as the human Prx [67].
To reduced, oxidized, and overoxidized species from purified proteins samples
Figure 9B
shows the SDS-PAGE result of
7. Conclusions
Acknowledgments
We acknowledge the financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo grants 07/50930-3, 16/10130-7, and 13/07937-8 (Redox Processes in Biomedicine [REDOXOMA]).
References
- 1.
Netto LES, Antunes F. The roles of peroxiredoxin and thioredoxin in hydrogen peroxide sensing and in signal transduction. Molecules and Cells. 2016; 39 :65-71. DOI: 10.14348/molcells.2016.2349 - 2.
Rhee SG. Overview on peroxiredoxin. Molecules and Cells. 2016; 39 :1-5. DOI: 10.14348/molcells.2016.2368 - 3.
Finkel T. Oxidant signals and oxidative stress. Current Opinion in Cell Biology. 2003; 15 :247-254. DOI: 10.1016/S0955-0674(03)00002-4 - 4.
Halliwell B, Gutteridge JMC. Free Radicals in Biology and Medicine. 5th ed. Oxford: Oxford University Press; 2015 - 5.
Kang SW, Rhee SG, Chang T-S, Jeong W, Choi MH. 2-Cys peroxiredoxin function in intracellular signal transduction: Therapeutic implications. Trends in Molecular Medicine. 2005; 11 :571-578. DOI: 10.1016/j.molmed.2005.10.006 - 6.
Molin M, Yang J, Hanzén S, Toledano MB, Labarre J, Nyström T. Life span extension and H(2)O(2) resistance elicited by caloric restriction require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae . Molecular Cell. 2011;43 :823-833. DOI: 10.1016/j.molcel.2011.07.027 - 7.
Vivancos AP, Castillo EA, Biteau B, Nicot C, Ayté J, Toledano MB, Hidalgo E. A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the antioxidant Pap1 pathway. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102 :8875-8880. DOI: 10.1073/pnas.0503251102 - 8.
Adimora NJ, Jones DP, Kemp ML. A model of redox kinetics implicates the thiol proteome in cellular hydrogen peroxide responses. Antioxidants and Redox Signaling. 2010;13:731-743. DOI: 10.1089/ars.2009.2968 - 9.
Perkins A, Nelson KJ, Parsonage D, Poole LB, Karplus PA. Peroxiredoxins: Guardians against oxidative stress and modulators of peroxide signaling. Trends in Biochemical Sciences. 2015; 40 :435-445. DOI: 10.1016/j.tibs.2015.05.001 - 10.
Tairum CA, Santos MC, Breyer CA, Geyer RR, Nieves CJ, Portillo-Ledesma S, Ferrer-Sueta G, Toledo JC, Toyama MH, Augusto O, Netto LES, de Oliveira MA. Catalytic Thr or Ser residue modulates structural switches in 2-cys peroxiredoxin by distinct mechanisms. Scientific Reports. 2016; 6 :33133. DOI: 10.1038/srep33133 - 11.
Jang HH, Lee KO, Chi YH, Jung BG, Park SK, Park JH, Lee JR, Lee SS, Moon JC, Yun JW, Choi YO, Kim WY, Kang JS, Cheong GW, Yun DJ, Rhee SG, Cho MJ, Lee SY. Two enzymes in one: Two yeast peroxiredoxins display oxidative stress-dependent switching from a peroxidase to a molecular chaperone function. Cell. 2004; 117 :625-635. DOI: 10.1016/j.cell.2004.05.002 - 12.
Hanzén S, Vielfort K, Yang J, Roger F, Andersson V, Zamarbide-Forés S, Andersson R, Malm L, Palais G, Biteau B, Liu B, Toledano MBB, Molin M, Nyström T. Lifespan control by redox-dependent recruitment of chaperones to misfolded proteins. Cell. 2016; 166 :140-151. DOI: 10.1016/j.cell.2016.05.006 - 13.
Chae HZ, Kim IH, Kim K, Rhee SG. Cloning, sequencing, and mutation of thiol-specific antioxidant gene of Saccharomyces cerevisiae . Journal of Biological Chemistry. 1993;268 :16815-16821 - 14.
Park SG, Cha MK, Jeong W, Kim IH. Distinct physiological functions of thiol peroxidase isoenzymes in Saccharomyces cerevisiae . Journal of Biological Chemistry. 2000;275 :5723-5732 - 15.
Pedrajas JR, Miranda-Vizuete A, Javanmardy N, Gustafsson JA, Spyrou G. Mitochondria of Saccharomyces cerevisiae contain one-conserved cysteine type peroxiredoxin with thioredoxin peroxidase activity. Journal of Biological Chemistry. 2000;275 :16296-16301. DOI: 10.1074/jbc.275.21.16296 - 16.
Ghaemmaghami S, Huh W, Bower K, Howson RW, Belle A, Dephoure N, O’Shea EK, Weissman JS. Global analysis of protein expression in yeast. Nature. 2003; 425 :737-741. DOI: 10.1038/nature02046 - 17.
Low FM, Hampton MB, Winterbourn CC. Peroxiredoxin 2 and peroxide metabolism in the erythrocyte. Antioxidants and Redox Signaling. 2008; 10 :1621-1630 DOI: 10.1089/ars.2008.2081 - 18.
Horta BB, Oliveira MA, Discola KF, Cussiol JRR, Netto LES. Structural and biochemical characterization of peroxiredoxin Qbeta from Xylella fastidiosa: Catalytic mechanism and high reactivity. Journal of Biological Chemistry. 2010; 285 :16051-16065. DOI: 10.1074/jbc.M109.094839 - 19.
Toledo JC, Audi R, Ogusucu R, Monteiro G, Netto LES, Augusto O. Horseradish peroxidase compound i as a tool to investigate reactive protein-cysteine residues: From quantification to kinetics. Free Radical Biology and Medicine. 2011; 50 :1032-1038. DOI: 10.1016/j.freeradbiomed.2011.02.020 - 20.
Reyes AM, Hugo M, Trostchansky A, Capece L, Radi R, Trujillo M. Oxidizing substrate specificity of Mycobacterium tuberculosis alkyl hydroperoxide reductase E: Kinetics and mechanisms of oxidation and overoxidation. Free Radical Biology and Medicine. 2011;51 :464-473. DOI: 10.1016/j.freeradbiomed.2011.04.023 - 21.
Tairum CA, de Oliveira MA, Horta BB, Zara FJ, Netto LES. Disulfide biochemistry in 2-cys peroxiredoxin: Requirement of Glu50 and Arg146 for the reduction of yeast Tsa1 by thioredoxin. Journal of Molecular Biology. 2012; 424 :28-41. DOI: 10.1016/j.jmb.2012.09.008 - 22.
Flohé L, Harris JR. Introduction. History of the peroxiredoxins and topical perspectives. Subcellular Biochemistry. 2007; 44 :1-25 - 23.
Flohé L, Toppo S, Cozza G, Ursini F. A comparison of thiol peroxidase mechanisms. Antioxidants and Redox Signaling. 2011; 15 :763-780. DOI: 10.1089/ars.2010.3397 - 24.
Hall A, Parsonage D, Poole LB, Karplus PA. Structural evidence that peroxiredoxin catalytic power is based on transition-state stabilization. Journal of Molecular Biology. 2010; 402 :194-209. DOI: 10.1016/j.jmb.2010.07.022 - 25.
Netto LES, de Oliveira MA, Tairum CA, da Silva Neto JF. Conferring specificity in redox pathways by enzymatic thiol/disulfide exchange reactions. Free Radical Research. 2016; 50 :206-245. DOI: 10.3109/10715762.2015.1120864 - 26.
Moon JC, Hah Y-S, Kim WY, Jung BG, Jang HH, Lee JR, Kim SY, Lee YM, Jeon MG, Kim CW, Cho MJ, Lee SY. Oxidative stress-dependent structural and functional switching of a human 2-Cys peroxiredoxin isotype II that enhances HeLa cell resistance to H2O2-induced cell death. Journal of Biological Chemistry. 2005; 280 :28775-28784. DOI: 10.1074/jbc.M505362200 - 27.
Toledano MB, Huang B. Microbial 2-Cys peroxiredoxins: Insights into their complex physiological roles. Molecules and Cells. 2016; 39 :31-39. DOI: 10.14348/molcells.2016.2326 - 28.
Banerjee M, Chakravarty D, Ballal A. Redox-dependent chaperone/peroxidase function of 2-Cys-Prx from the cyanobacterium Anabaena PCC7120: Role in oxidative stress tolerance. BMC Plant Biology. 2015; 15 :60. DOI: 10.1186/s12870-015-0444-2 - 29.
König J, Galliardt H, Jütte P, Schäper S, Dittmann L, Dietz K-J. The conformational bases for the two functionalities of 2-cysteine peroxiredoxins as peroxidase and chaperone. Journal of Experimental Botany. 2013; 64 :3483-3497. DOI: 10.1093/jxb/ert184 - 30.
Pan Y, Jin J-H, Yu Y, Wang J. Significant enhancement of hPrx1 chaperone activity through lysine acetylation. Chembiochem. 2014; 15 :1773-1776. DOI: 10.1002/cbic.201402164 - 31.
Biteau B, Labarre J, Toledano MB. ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin. Nature. 2003;425 :980-984. DOI: 10.1038/nature02075 - 32.
Mishra M, Jiang H, Wu L, Chawsheen HA, Wei Q. The sulfiredoxin-peroxiredoxin (Srx-Prx) axis in cell signal transduction and cancer development. Cancer Letters. 2015; 366 :150-159. DOI: 10.1016/j.canlet.2015.07.002 - 33.
Wood Z, Poole LB, Karplus PA. Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science. 2003; 300 :650-653. DOI: 10.1126/science.1080405 - 34.
Wood ZA, Schro E, Harris JR, Poole LB. Structure, mechanism and regulation of peroxiredoxins. Trends in Biochemical Sciences. 2003; 28 :00003-00008 - 35.
Pascual MB, Mata-cabana A, Florencio FJ, Lindahl M, Cejudo FJ. Overoxidation of 2-Cys peroxiredoxin in prokaryotes. Journal of Biological Chemistry. 2010; 285 :34485-34492. DOI: 10.1074/jbc.M110.160465 - 36.
Tachibana T, Okazaki S, Murayama A, Naganuma A, Nomoto A, Kuge S. A major peroxiredoxin-induced activation of Yap1 transcription factor is mediated by reduction-sensitive disulfide bonds and reveals a low level of transcriptional activation. Journal of Biological Chemistry. 2009; 284 :4464-4472. DOI: 10.1074/jbc.M807583200 - 37.
Sobotta MC, Liou W, Stöcker S, Talwar D, Oehler M, Ruppert T, Scharf AND, Dick TP. Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nature Chemical Biology. 2015; 11 :64-70. DOI: 10.1038/nchembio.1695 - 38.
Cao J, Schulte J, Knight A, Leslie NR, Zagozdzon A, Bronson R, Manevich Y, Beeson C, Neumann CA. Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity. EMBO Journal. 2009; 28 :1505-1517. DOI: 10.1038/emboj.2009.101 - 39.
Berndt C, Lillig CH, Holmgren A. Thiol-based mechanisms of the thioredoxin and glutaredoxin systems: Implications for diseases in the cardiovascular system. American Journal of Physiology—Heart and Circulatory Physiology. 2007; 292 :H1227-H1236. DOI: 10.1152/ajpheart.01162.2006 - 40.
Day AM, Brown JD, Taylor SR, Rand JD, Morgan BA, Veal EA. Article Inactivation of a peroxiredoxin by hydrogen peroxide is critical for thioredoxin-mediated repair of oxidized proteins and cell survival. Molecular Cell. 2012; 45 :398-408. DOI: 10.1016/j.molcel.2011.11.027 - 41.
Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, Kawabata M, Miyazono K, Ichijo H. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO Journal. 1998; 17 :2596-2606. DOI: 10.1093/emboj/17.9.2596 - 42.
Napetschnig J, Wu H. Molecular basis of NF-κB signaling. Annual Review of Biophysics. 2013; 42 :443-468. DOI: 10.1146/annurev-biophys-083012-130338 - 43.
Matthews JR, Wakasugi N, Virelizier JL, Yodoi J, Hay RT. Thioredoxin regulates the DNA binding activity of NF-kappa B by reduction of a disulphide bond involving cysteine 62. Nucleic Acids Research. 1992; 20 :3821-3830 - 44.
Lee JY, Jung HJ, Song IS, Williams MS, Choi C, Rhee SG, Kim J, Kang SW. Protective role of cytosolic 2-cys peroxiredoxin in the TNF-alpha-induced apoptotic death of human cancer cells. Free Radical Biology and Medicine. 2009; 47 :1162-1171. DOI: 10.1016/j.freeradbiomed.2009.07.027 - 45.
Choi MH, Lee IK, Kim GW, Kim BU, Han Y-H, Yu D-Y, Park HS, Kim KY, Lee JS, Choi C, Bae YS, Lee BI, Rhee SG, Kang SW. Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II. Nature. 2005;435:347-353. DOI: 10.1038/nature03587 - 46.
Miki H, Funato Y. Regulation of intracellular signalling through cysteine oxidation by reactive oxygen species. Journal of Biochemistry. 2012; 151 :255-261. DOI: 10.1093/jb/mvs006 - 47.
Liu C-X, Yin Q-Q, Zhou H-C, Wu Y-L, Pu J-X, Xia L, Liu W, Huang X, Jiang T, Wu M-X, He L-C, Zhao Y-X, Wang X-L, Xiao W-L, Chen H-Z, Zhao Q, Zhou A-W, Wang L-S, Sun H-D, Chen G-Q. Adenanthin targets peroxiredoxin I and II to induce differentiation of leukemic cells. Nature Chemical Biology. 2012; 8 :486-493. DOI: 10.1038/nchembio.935 - 48.
Liu C-X, Zhou H-C, Yin Q-Q, Wu Y-L, Chen G-Q. Targeting peroxiredoxins against leukemia. Experimental Cell Research. 2013; 319 :170-176. DOI: 10.1016/j.yexcr.2012.06.013 - 49.
Dunlap JC. Molecular bases for circadian clocks. Cell. 1999; 96 :271-290. DOI: 10.1016/S0092-8674(00)80566-8 - 50.
Woelfle MA, Ouyang Y, Phanvijhitsiri K, Johnson CH. The adaptive value of circadian clocks: An experimental assessment in Cyanobacteria. Current Biology. 2004; 14 :1481-1486. DOI: 10.1016/j.cub.2004.08.023 - 51.
O’Neill JS, van Ooijen G, Dixon LE, Troein C, Corellou F, Bouget F-Y, Reddy AB, Millar AJ. Circadian rhythms persist without transcription in a eukaryote. Nature. 2011; 469 :554-558. DOI: 10.1038/nature09654 - 52.
Causton HC, Feeney KA, Ziegler CA, O’Neill JS. Metabolic cycles in yeast share features conserved among circadian rhythms. Current Biology. 2015; 25 :1056-1062. DOI: 10.1016/j.cub.2015.02.035 - 53.
Wijnen H, Young MW. Interplay of circadian clocks and metabolic rhythms. Annual Review of Genetics. 2006; 40 :409-448. DOI: 10.1146/annurev.genet.40.110405.090603 - 54.
Edgar RS, Green EW, Zhao Y, van Ooijen G, Olmedo M, Qin X, Xu Y, Pan M, Valekunja UK, Feeney KA, Maywood ES, Hastings MH, Baliga NS, Merrow M, Millar AJ, Johnson CH, Kyriacou CP, O’Neill JS, Reddy AB. Peroxiredoxins are conserved markers of circadian rhythms. Nature. 2012; 485 :459-464. DOI: 10.1038/nature11088 - 55.
Hoyle NP, O’Neill JS. Oxidation-reduction cycles of peroxiredoxin proteins and nontranscriptional aspects of timekeeping. Biochemistry. 2015; 54 :184-193. DOI: 10.1021/bi5008386 - 56.
O’Neill JS, Reddy AB. Circadian clocks in human red blood cells. Nature. 2011; 469 :498-503. DOI: 10.1038/nature09702 - 57.
Fonseca Costa SS, Ripperger JA. Impact of the circadian clock on the aging process. Frontiers in Neurology. 2015; 6 :1-5. DOI: 10.3389/fneur.2015.00043 - 58.
Nyström T, Yang J, Molin M. Peroxiredoxins, gerontogenes linking aging to genome instability and cancer. Genes and Development. 2012; 26 :2001-2008. DOI: 10.1101/gad.200006.112 - 59.
Timmermann B, Jarolim S, Rußmayer H, Kerick M, Michel S, Krüger A, Bluemlein K, Laun P, Grillari J, Lehrach H, Breitenbach M, Ralser M. A new dominant peroxiredoxin allele identified by whole-genome re-sequencing of random mutagenized yeast causes oxidant-resistance and premature aging. Aging (Albany NY). 2010; 2 :475-486. DOI: 10.18632/aging.100187 - 60.
Kaeberlein M, Hu D, Kerr EO, Tsuchiya M, Westman EA, Dang N, Fields S, Kennedy BK. Increased life span due to calorie restriction in respiratory-deficient yeast. PLoS Genetics. 2005; 1 :e69. DOI: 10.1371/journal.pgen.0010069 - 61.
Huang M-E, Kolodner RD. A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage. Molecular Cell. 2005;17 :709-720. DOI: 10.1016/j.molcel.2005.02.008 - 62.
Lu J, Vallabhaneni H, Yin J, Liu Y. Deletion of the major peroxiredoxin Tsa1 alters telomere length homeostasis. Aging Cell. 2013; 12 :635-644. DOI: 10.1111/acel.12085 - 63.
de Lange T. How shelterin solves the telomere end-protection problem. Cold Spring Harbor Symposia on Quantitative Biology. 2010; 75 :167-177. DOI: 10.1101/sqb.2010.75.017 - 64.
Matte A, Bertoldi M, Mohandas N, An X, Bugatti A, Brunati AM, Rusnati M, Tibaldi E, Siciliano A, Turrini F, Perrotta S, De Franceschi L. Membrane association of peroxiredoxin-2 in red cells is mediated by the N-terminal cytoplasmic domain of band 3. Free Radical Biology and Medicine. 2013; 55 :27-35. DOI: 10.1016/j.freeradbiomed.2012.10.543 - 65.
Cho C-S, Yoon HJ, Kim JY, Woo HA, Rhee SG. Circadian rhythm of hyperoxidized peroxiredoxin II is determined by hemoglobin autoxidation and the 20S proteasome in red blood cells. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111 :12043-12048. DOI: 10.1073/pnas.1401100111 - 66.
Saccoccia F, Di Micco P, Boumis G, Brunori M, Koutris I, Miele AE, Morea V, Sriratana P, Williams DL, Bellelli A, Angelucci F. Moonlighting by different stressors: Crystal structure of the chaperone species of a 2-Cys peroxiredoxin. Structure. 2012; 20 :429-439. DOI: 10.1016/j.str.2012.01.004 - 67.
Radjainia M, Venugopal H, Desfosses A, Phillips AJ, Yewdall NA, Hampton MB, Gerrard JA, Mitra AK. Cryo-electron microscopy structure of human peroxiredoxin-3 filament reveals the assembly of a putative chaperone. Structure. 2015; 23 :912-920. DOI: 10.1016/j.str.2015.03.019 - 68.
Nelson KJ, Parsonage D, Karplus PA, Poole LB. Evaluating peroxiredoxin sensitivity toward inactivation by peroxide substrates. Methods in Enzymology. 2013; 527 :21-40. DOI: 10.1016/B978-0-12-405882-8.00002-7 - 69.
Cox AG, Pearson AG, Pullar JM, Onsson TJJ, Lowther WT, Winterbourn CC, Hampton MB. Mitochondrial peroxiredoxin 3 is more resilient to hyperoxidation than cytoplasmic peroxiredoxins. Movie. 2009; 58 :51-58. DOI: 10.1042/BJ20090242 - 70.
Woo HA, Kang SW, Kim HK, Yang KS, Chae HZ, Rhee SG. Reversible oxidation of the active site cysteine of peroxiredoxins to cysteine sulfinic acid: Immunoblot detection with antibodies specific for the hyperoxidized cysteine-containing sequence. Journal of Biological Chemistry. 2003; 278 :47361-47364. DOI: 10.1074/jbc.C300428200