S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Journal Papers (저널논문_의학과)
Down syndrome critical region 1 enhances the proteolytic cleavage of calcineurin
- Lee, Ji-Eun; Jang, Hyonchol; Cho, Eun-Jung; Youn, Hong-Duk
- Issue Date
- EXPERIMENTAL AND MOLECULAR MEDICINE; Vol.41 7; 471-477
- calcineurin; Down syndrome; fibroblasts; RCAN1 protein, human; oxidative stress; hydrogen peroxide; DSCR1 protein, mouse
- Down syndrome critical region 1 (DSCR1), an oxidative stress-response gene, interacts with calcineurin and represses its phosphatase activity. Recently it was shown that hydrogen peroxide inactivates calcineurin by proteolytic cleavage. Based on these facts, we investigated whether oxidative stress affects DSCR1-mediated inactivation of calcineurin. We determined that overexpression of DSCR1 leads to increased proteolytic cleavage of calcineurin. Convertselly, knockdown of DSCR1 abolished calcineurin cleavage upon treatment with hydrogen peroxide. The PXIIXT motif in the COOH-terminus of DSCR1 is responsible for both binding and cleavage of calcineurin. The knockdown of overexpressed DSCR1 in DS fibroblast cells also abrogated calcineurin proteolysis by hydrogen peroxide. These results suggest that DSCR1 has the ability to inactivate calcineurin by inducing proteolytic cleavage of calcineurin upon oxidative stress.