title: Peroxiredoxin II restrains DNA damage-induced death in cancer cells by positively regulating JNK-dependent DNA repair.
abstract: The 2-Cys peroxiredoxins (Prx) belong to a family of antioxidant enzymes that detoxify reactive oxygen and nitrogen species and are distributed throughout the intracellular and extracellular compartments. However, the presence and role of 2-Cys Prxs in the nucleus have not been studied. This study demonstrates that the PrxII located in the nucleus protects cancer cells from DNA damage-induced cell death. Although the two cytosolic 2-Cys Prxs, PrxI and PrxII, were found in the nucleus, only PrxII knockdown selectively and markedly increased cell death in the cancer cells treated with DNA-damaging agents. The increased death was completely reverted by the nuclearly targeted expression of PrxII in an activity-independent manner. Furthermore, the antioxidant butylated hydroxyanisole did not influence the etoposide-induced cell death. Mechanistically, the knockdown of Prx II expression impaired the DNA repair process by reducing the activation of the JNK/c-Jun pathway. These results suggest that PrxII is likely to be attributed to a tumor survival factor positively regulating JNK-dependent DNA repair with its inhibition possibly sensitizing cancer cells to chemotherapeutic agents.
authors.affiliation: From the Division of Life and Pharmaceutical Sciences.
authors.forename: Kyung Wha
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Center for Cell Signaling and Drug Discovery Research, and.
authors.forename: Doo Jae
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: From the Division of Life and Pharmaceutical Sciences.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Center for Cell Signaling and Drug Discovery Research, and.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Kang
authors.affiliation: From the Division of Life and Pharmaceutical Sciences,; Center for Cell Signaling and Drug Discovery Research, and; Department of Life Sciences, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Jongbum
authors.initials: J
authors.lastname: Kwon
authors.affiliation: From the Division of Life and Pharmaceutical Sciences,; Center for Cell Signaling and Drug Discovery Research, and; Department of Life Sciences, Ewha Womans University, Seoul 120-750, Korea. Electronic address: kangsw@ewha.ac.kr.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D005047:Etoposide / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D016755:Proto-Oncogene Proteins c-jun; D005047:Etoposide; C086065:PRDX2 protein, human; D054464:Peroxiredoxins; D048670:MAP Kinase Kinase 4