Figure 7. A model illustrating the propose role of APE1-PRDX1 interaction in regulating gene expression.

Under normal metabolism, the reduced form of PRDX1_Red decomposes the endogenously produced H₂O₂ to water and in turn becomes oxidized. The oxidized PRDX1_Oxd is regenerated to the reduced form by the interaction with the reduced form of APE1 _Red. In this scheme, APE1_Oxd is believed to be regenerated by thioredoxin I (TRX1). In the absence of PRDX1, there is a built up of H₂O₂ in the cells leading to the oxidation of NF-κB, which is set free from its inhibitor IKK and translocates to the nucleus. The oxidized NF-κB_Oxd has a redox cysteine (Cys62) that must be reduced in order for this transcription factor to bind to the promoter sequence of target genes such as IL-8. In the PRDX1 knockdown cells, APE1 is poised to reduce NF-κB resulting in the induction of IL-8 gene expression.