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.

Global irradiation effects, stem cell genes and rare transcripts in the planarian transcriptome

“…Interestingly, when the human embryonic stem cell hesc-0238 DGE transcriptome was compared to the ES modules, the number of genes found in common was not in higher proportion: 5% (248 genes) of the hesc preferentially expressed genes. This analysis highlighted several promising potentially conserved stem cell candidate genes, for example PRDX2, an antioxidant enzyme which has been involved in cancer cell survival (Lee et al, 2011), PLOD3, a collagen lysyl hydroxylase over secreted by pancreatic cancer cells (Schiarea et al, 2010), and an antisense to the actin modulating factor cofilin CFL1.…”

Peroxiredoxin-2 Represses Melanoma Metastasis by Increasing E-Cadherin/β-Catenin Complexes in Adherens Junctions

“…These viruses were mainly used for the Prx2 overexpression in the SK-MEL cells. Second, the production of retrovirus encoding myc-tagged human Prx2 WT and inactive CS mutant (Cys51Ser/Cys173Ser) using the Retro-X Q vector system was previously described (16). The viral titers were determined (1 Â 10 6 viral particles/mL) and the aliquots were stored at À70 C. For retroviral infection, the viral aliquots were thawed in warm water bath and mixed with 10 mg/mL polybrene.…”

Molecular Basis for the Resistance of Human Mitochondrial 2-Cys Peroxiredoxin 3 to Hyperoxidation

“…Although this function was originally thought to be primarily protective in nature, Prxs also play a key role in modulating H 2 O 2 -mediated cell signaling in normal and pathophysiological contexts, including cell growth, differentiation, adrenal steroidogenesis, neurodegeneration, and cancer (1)(2)(3)(4)(5). Human cells contain six Prx isoforms with differences in subcellular localization and the content of Cys residues (6).…”