PRDX3 explained

Thioredoxin-dependent peroxide reductase, mitochondrial is an enzyme that in humans is encoded by the PRDX3 gene.^{[1] [2] [3]} It is a member of the peroxiredoxin family of antioxidant enzymes.

Function

This gene encodes a protein with antioxidant function and is localized in the mitochondrion. This gene shows significant nucleotide sequence similarity to the gene coding for the C22 subunit of Salmonella typhimurium alkylhydroperoxide reductase. Expression of this gene product in E. coli deficient in the C22-subunit gene rescued resistance of the bacteria to alkylhydroperoxide. The human and mouse genes are highly conserved, and they map to the regions syntenic between mouse and human chromosomes. Sequence comparisons with recently cloned mammalian homologues suggest that these genes consist of a family that is responsible for regulation of cellular proliferation, differentiation, and antioxidant functions. Two transcript variants encoding two different isoforms have been found for this gene.^[3]

Interactions

PRDX3 has been shown to interact with MAP3K13.^[4]

Clinical significance

It has been demonstrated that serum peroxiredoxin 3 can be a valuable biomarker for the diagnosis and assessment of hepatocellular carcinoma^[5] It has been shown that peroxiredoxin proteins protect MCF-7 breast cancer cells against doxorubicin-mediated toxicity.^[6] Additionally, it has been shown that peroxiredoxin 3 is overexpressed in prostate cancer and promotes cancer cell survival by defending cells against the damages incurred by oxidative stress.^[7]

Further reading

• Hochstrasser DF, Frutiger S, Paquet N, Bairoch A, Ravier F, Pasquali C, Sanchez JC, Tissot JD, Bjellqvist B, Vargas R . Human liver protein map: a reference database established by microsequencing and gel comparison . Electrophoresis . 13 . 12 . 992–1001 . 1992 . 1286669 . 10.1002/elps.11501301201 . 23518983 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Shih SF, Wu YH, Hung CH, Yang HY, Lin JY . Abrin triggers cell death by inactivating a thiol-specific antioxidant protein . J. Biol. Chem. . 276 . 24 . 21870–7 . 2001 . 11285261 . 10.1074/jbc.M100571200 . free .
• Suzuki H, Fukunishi Y, Kagawa I, Saito R, Oda H, Endo T, Kondo S, Bono H, Okazaki Y, Hayashizaki Y . Protein-protein interaction panel using mouse full-length cDNAs . Genome Res. . 11 . 10 . 1758–65 . 2001 . 11591653 . 311163 . 10.1101/gr.180101 .
• 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 . Journal of Neural Transmission. Supplementum . 61 . 223–35 . 2001 . 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 . J. Biol. Chem. . 277 . 22 . 19396–401 . 2002 . 11904290 . 10.1074/jbc.M106585200 . free .
• Wonsey DR, Zeller KI, Dang CV . The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation . Proc. Natl. Acad. Sci. U.S.A. . 99 . 10 . 6649–54 . 2002 . 12011429 . 124457 . 10.1073/pnas.102523299 . 2002PNAS...99.6649W . 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 . Biochem. J. . 366 . Pt 3 . 777–85 . 2002 . 12059788 . 1222825 . 10.1042/BJ20020525 .
• Shen C, Nathan C . Nonredundant antioxidant defense by multiple two-cysteine peroxiredoxins in human prostate cancer cells . Mol. Med. . 8 . 2 . 95–102 . 2002 . 12080185 . 2039972 . 10.1007/BF03402079.
• Masaki M, Ikeda A, Shiraki E, Oka S, Kawasaki T . Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically . Eur. J. Biochem. . 270 . 1 . 76–83 . 2003 . 12492477 . 10.1046/j.1432-1033.2003.03363.x .
• Choi JH, Kim TN, Kim S, Baek SH, Kim JH, Lee SR, Kim JR . Overexpression of mitochondrial thioredoxin reductase and peroxiredoxin III in hepatocellular carcinomas . Anticancer Res. . 22 . 6A . 3331–5 . 2003 . 12530083 .
• Krapfenbauer K, Engidawork E, Cairns N, Fountoulakis M, Lubec G . Aberrant expression of peroxiredoxin subtypes in neurodegenerative disorders . Brain Res. . 967 . 1–2 . 152–60 . 2003 . 12650976 . 10.1016/S0006-8993(02)04243-9 . 854144 .
• Chang TS, Cho CS, Park S, Yu S, Kang SW, Rhee SG . Peroxiredoxin III, a mitochondrion-specific peroxidase, regulates apoptotic signaling by mitochondria . J. Biol. Chem. . 279 . 40 . 41975–84 . 2004 . 15280382 . 10.1074/jbc.M407707200 . free .
• Liu L, Yang C, Yuan J, Chen X, Xu J, Wei Y, Yang J, Lin G, Yu L . RPK118, a PX domain-containing protein, interacts with peroxiredoxin-3 through pseudo-kinase domains . Mol. Cells . 19 . 1 . 39–45 . 2005 . 10.1016/S1016-8478(23)13134-7 . 15750338 . free .

Notes and References

1. Tsuji K, Copeland NG, Jenkins NA, Obinata M . Mammalian antioxidant protein complements alkylhydroperoxide reductase (ahpC) mutation in Escherichia coli . Biochem. J. . 307 . 2 . 377–81 . May 1995 . 7733872 . 1136659 . 10.1042/bj3070377.
2. Watabe S, Hiroi T, Yamamoto Y, Fujioka Y, Hasegawa H, Yago N, Takahashi SY . SP-22 is a thioredoxin-dependent peroxide reductase in mitochondria . Eur. J. Biochem. . 249 . 1 . 52–60 . Dec 1997 . 9363753 . 10.1111/j.1432-1033.1997.t01-1-00052.x .
3. Web site: Entrez Gene: PRDX3 peroxiredoxin 3.
4. Masaki M, Ikeda A, Shiraki E, Oka S, Kawasaki T . Mixed lineage kinase LZK and antioxidant protein-1 activate NF-kappaB synergistically . Eur. J. Biochem. . 270 . 1 . 76–83 . Jan 2003 . 12492477 . 10.1046/j.1432-1033.2003.03363.x .
5. Shi L, Wu LL, Yang JR, Chen XF, Zhang Y, Chen ZQ, Liu CL, Chi SY, Zheng JY, Huang HX, Yu FJ, Lin XY . Serum peroxiredoxin3 is a useful biomarker for early diagnosis and assessment of prognosis of hepatocellular carcinoma in Chinese patients . Asian Pacific Journal of Cancer Prevention . 15 . 7 . 2014 . 24815434 . 2979–86 . 10.7314/apjcp.2014.15.7.2979. free .
6. McDonald C, Muhlbauer J, Perlmutter G, Taparra K, Phelan SA . Peroxiredoxin proteins protect MCF-7 breast cancer cells from doxorubicin-induced toxicity . International Journal of Oncology . 45 . 1 . Jul 2014 . 24789097 . 10.3892/ijo.2014.2398 . 219–26. free .
7. Whitaker HC, Patel D, Howat WJ, Warren AY, Kay JD, Sangan T, Marioni JC, Mitchell J, Aldridge S, Luxton HJ, Massie C, Lynch AG, Neal DE . Peroxiredoxin-3 is overexpressed in prostate cancer and promotes cancer cell survival by protecting cells from oxidative stress . British Journal of Cancer . 109 . 4 . Aug 2013 . 23880827 . 10.1038/bjc.2013.396 . 983–93 . 3749568.