Hydrogen peroxide-induced MAPK activation causes the increase of RCAN1 (DSCR1) protein expression

The Down syndrome critical region 1 (DSCR1) gene encodes a regulator of calcineurin 1 (RCAN1), which is overexpressed in the patients with Down syndrome. In this study, we found that the protein expression of RCAN1 was increased by the hydrogen peroxide (H2O2). The increase of RCAN1 expression by H2O2 was blocked by the treatment with anti-oxidants and inhibitors of mitogen-activated protein kinases (MAPKs), indicating that this increase was caused by the generation of reactive oxygen species and activation of MAPKs. In addition, we found that the phosphorylation of RCAN1 by H2O2 caused an increase of RCAN1 expression by increasing of the half-life of the protein. Our results provide the evidence that H2O2 acts as an important regulator in the control of RCAN1 protein expression through phosphorylation.