Peroxiredoxin 1 Explained

Peroxiredoxin-1 is a protein that in humans is encoded by the PRDX1 gene.^{[1] [2]}

Function

This gene encodes a member of the peroxiredoxin family of antioxidant enzymes, which reduce hydrogen peroxide and alkyl hydroperoxides.^[3] The encoded protein may play an antioxidant protective role in cells, and may contribute to the antiviral activity of CD8(+) T-cells. This protein may have a proliferative effect and play a role in cancer development or progression. Three transcript variants encoding the same protein have been identified for this gene.^[2]

Interactions

Peroxiredoxin 1 has been shown to interact with PRDX4.^[4] A chemoproteomic approach has revealed that peroxiredoxin 1 is the main target of theonellasterone.^[5]

Clinical significance

As enzymes that combat oxidative stress, peroxiredoxins play an important role in health and disease.^[6] Peroxiredoxin 1 and peroxiredoxin 2 have been shown to be released by some cells when stimulated by LPS or TNF-alpha.^[7] The released peroxiredoxin can then act to produce inflammatory cytokines.^[8] In some types of cancer, peroxiredoxin 1 has been determined to act as a tumor suppressor and other studies show that peroxiredoxin 1 is overexpressed in certain human cancers.^[10] A recent study has found that peroxiredoxin 1 may play a role in tumorigenesis by regulating the mTOR/p70S6K pathway in esophageal squamous cell carcinoma.^[11] It has also been shown that peroxiredoxin 1 may be an important player in the pathogenesis of acute respiratory distress syndrome because of its role in promoting inflammation.^[13]

Further reading

• Wood ZA, Schröder E, Robin Harris J, Poole LB . Structure, mechanism and regulation of peroxiredoxins . Trends in Biochemical Sciences . 28 . 1 . 32–40 . Jan 2003 . 12517450 . 10.1016/S0968-0004(02)00003-8 .
• Sauri H, Butterfield L, Kim A, Shau H . Antioxidant function of recombinant human natural killer enhancing factor . Biochemical and Biophysical Research Communications . 208 . 3 . 964–9 . Mar 1995 . 7702627 . 10.1006/bbrc.1995.1428 .
• Shau H, Butterfield LH, Chiu R, Kim A . Cloning and sequence analysis of candidate human natural killer-enhancing factor genes . Immunogenetics . 40 . 2 . 129–34 . 1994 . 8026862 . 10.1007/BF00188176 . 7778993 .
• Kawai S, Takeshita S, Okazaki M, Kikuno R, Kudo A, Amann E . Cloning and characterization of OSF-3, a new member of the MER5 family, expressed in mouse osteoblastic cells . Journal of Biochemistry . 115 . 4 . 641–3 . Apr 1994 . 8089076 . 10.1093/oxfordjournals.jbchem.a124388.
• Shau H, Kim A . Identification of natural killer enhancing factor as a major antioxidant in human red blood cells . Biochemical and Biophysical Research Communications . 199 . 1 . 83–8 . Feb 1994 . 8123050 . 10.1006/bbrc.1994.1197 .
• Prospéri MT, Apiou F, Dutrillaux B, Goubin G . Organization and chromosomal assignment of two human PAG gene loci: PAGA encoding a functional gene and PAGB a processed pseudogene . Genomics . 19 . 2 . 236–41 . Jan 1994 . 8188254 . 10.1006/geno.1994.1053 .
• Wen ST, Van Etten RA . The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity . Genes & Development . 11 . 19 . 2456–67 . Oct 1997 . 9334312 . 316562 . 10.1101/gad.11.19.2456 .
• Jin DY, Chae HZ, Rhee SG, Jeang KT . Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation . The Journal of Biological Chemistry . 272 . 49 . 30952–61 . Dec 1997 . 9388242 . 10.1074/jbc.272.49.30952 . free .
• Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, Weitz JI, Austin RC . Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells . Blood . 94 . 3 . 959–67 . Aug 1999 . 10419887 . 10.1182/blood.V94.3.959.415k20_959_967.
• Yanagawa T, Ishikawa T, Ishii T, Tabuchi K, Iwasa S, Bannai S, Omura K, Suzuki H, Yoshida H . Peroxiredoxin I expression in human thyroid tumors . Cancer Letters . 145 . 1–2 . 127–32 . Oct 1999 . 10530780 . 10.1016/S0304-3835(99)00243-8 .
• Noh DY, Ahn SJ, Lee RA, Kim SW, Park IA, Chae HZ . Overexpression of peroxiredoxin in human breast cancer . Anticancer Research . 21 . 3B . 2085–90 . 2001 . 11497302 .
• Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q, Cai T, Zhang X, Xiao HS, Qu J, Liu F, Huang QH, Cheng ZH, Li NG, Du JJ, Hu W, Shen KT, Lu G, Fu G, Zhong M, Xu SH, Gu WY, Huang W, Zhao XT, Hu GX, Gu JR, Chen Z, Han ZG . Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver . Proceedings of the National Academy of Sciences of the United States of America . 98 . 26 . 15089–94 . Dec 2001 . 11752456 . 64988 . 10.1073/pnas.241522398 . 2001PNAS...9815089X . free .
• Book: Kim SH, Fountoulakis M, Cairns N, Lubec G . Protein Expression in Down Syndrome Brain . Protein levels of human peroxiredoxin subtypes in brains of patients with Alzheimer's disease and Down Syndrome . 2001 . Journal of Neural Transmission. Supplementum . 61 . 223–35 . 11771746 . 10.1007/978-3-7091-6262-0_18 . 978-3-211-83704-7 .
• Rabilloud T, Heller M, Gasnier F, Luche S, Rey C, Aebersold R, Benahmed M, Louisot P, Lunardi J . Proteomics analysis of cellular response to oxidative stress. Evidence for in vivo overoxidation of peroxiredoxins at their active site . The Journal of Biological Chemistry . 277 . 22 . 19396–401 . May 2002 . 11904290 . 10.1074/jbc.M106585200 . free .
• Chang TS, Jeong W, Choi SY, Yu S, Kang SW, Rhee SG . Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation . The Journal of Biological Chemistry . 277 . 28 . 25370–6 . Jul 2002 . 11986303 . 10.1074/jbc.M110432200 . free .
• Wagner E, Luche S, Penna L, Chevallet M, Van Dorsselaer A, Leize-Wagner E, Rabilloud T . A method for detection of overoxidation of cysteines: peroxiredoxins are oxidized in vivo at the active-site cysteine during oxidative stress . The Biochemical Journal . 366 . Pt 3 . 777–85 . Sep 2002 . 12059788 . 1222825 . 10.1042/BJ20020525 .
• Shen C, Nathan C . Nonredundant antioxidant defense by multiple two-cysteine peroxiredoxins in human prostate cancer cells . Molecular Medicine . 8 . 2 . 95–102 . Feb 2002 . 12080185 . 2039972 . 10.1007/BF03402079.
• Yang KS, Kang SW, Woo HA, Hwang SC, Chae HZ, Kim K, Rhee SG . Inactivation of human peroxiredoxin I during catalysis as the result of the oxidation of the catalytic site cysteine to cysteine-sulfinic acid . The Journal of Biological Chemistry . 277 . 41 . 38029–36 . Oct 2002 . 12161445 . 10.1074/jbc.M206626200 . free .
• Geiben-Lynn R, Kursar M, Brown NV, Addo MM, Shau H, Lieberman J, Luster AD, Walker BD . HIV-1 antiviral activity of recombinant natural killer cell enhancing factors, NKEF-A and NKEF-B, members of the peroxiredoxin family . The Journal of Biological Chemistry . 278 . 3 . 1569–74 . Jan 2003 . 12421812 . 10.1074/jbc.M209964200 . free .

Notes and References

1. Prospéri MT, Ferbus D, Karczinski I, Goubin G . A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins . The Journal of Biological Chemistry . 268 . 15 . 11050–6 . May 1993 . 10.1016/S0021-9258(18)82090-7 . 8496166 . free .
2. Web site: Entrez Gene: PRDX1 peroxiredoxin 1.
3. Wu . C . Dai . H . Yan . L . Liu . T . Cui . C . Chen . T . Li . H . Sulfonation of the resolving cysteine in human peroxiredoxin 1: A comprehensive analysis by mass spectrometry. . Free Radical Biology & Medicine . July 2017 . 108 . 785–792 . 10.1016/j.freeradbiomed.2017.04.341 . 28450148. 5564515 .
4. Jin DY, Chae HZ, Rhee SG, Jeang KT . Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation . The Journal of Biological Chemistry . 272 . 49 . 30952–61 . Dec 1997 . 9388242 . 10.1074/jbc.272.49.30952 . free .
5. Margarucci L, Monti MC, Tosco A, Esposito R, Zampella A, Sepe V, Mozzicafreddo M, Riccio R, Casapullo A . Theonellasterone, a steroidal metabolite isolated from a Theonella sponge, protects peroxiredoxin-1 from oxidative stress reactions . Chemical Communications . 51 . 9 . 1591–3 . Jan 2015 . 25503482 . 10.1039/c4cc09205h . 11393982 .
6. El Eter E, Al-Masri AA . Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus . Brazilian Journal of Medical and Biological Research . 48 . 5 . 465–9 . May 2015 . 25742636 . 4445671 . 10.1590/1414-431X20144142 .
7. Mullen L, Hanschmann EM, Lillig CH, Herzenberg LA, Ghezzi P . Cysteine Oxidation Targets Peroxiredoxins 1 and 2 for Exosomal Release through a Novel Mechanism of Redox-Dependent Secretion . Molecular Medicine . 21 . 98–108 . 2015 . 1 . 25715249 . 4461588 . 10.2119/molmed.2015.00033 .
8. Cai CY, Zhai LL, Wu Y, Tang ZG . Expression and clinical value of peroxiredoxin-1 in patients with pancreatic cancer . European Journal of Surgical Oncology . 41 . 2 . 228–35 . Feb 2015 . 25434328 . 10.1016/j.ejso.2014.11.037 .
9. The levels of peroxiredoxin 1 are elevated in pancreatic cancer and it can potentially act as a marker for the diagnosis and prognosis of this disease.^[8]
10. Gong F, Hou G, Liu H, Zhang M . Peroxiredoxin 1 promotes tumorigenesis through regulating the activity of mTOR/p70S6K pathway in esophageal squamous cell carcinoma . Medical Oncology . 32 . 2 . 455 . Feb 2015 . 25579166 . 10.1007/s12032-014-0455-0 . 5123492 .
11. Jiang H, Wu L, Mishra M, Chawsheen HA, Wei Q . Expression of peroxiredoxin 1 and 4 promotes human lung cancer malignancy . American Journal of Cancer Research . 4 . 5 . 445–60 . 2014 . 25232487 . 4163610 .
12. The expression patterns of peroxiredoxin 1 along with peroxiredoxin 4 are involved in human lung cancer malignancy.^[11]
13. Liu D, Mao P, Huang Y, Liu Y, Liu X, Pang X, Li Y . Proteomic analysis of lung tissue in a rat acute lung injury model: identification of PRDX1 as a promoter of inflammation . Mediators of Inflammation . 2014 . 1–14 . 2014 . 25024510 . 4082880 . 10.1155/2014/469358 . free .