Down syndrome critical region 1 enhances the proteolytic cleavage of calcineurin

• Published in: Experimental & molecular medicine Vol. 41; no. 7; pp. 471 - 477
• Main Authors: Lee, Ji-Eun, Jang, Hyonchol, Cho, Eun-Jung, Youn, Hong-Duk
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.07.2009; Springer Nature B.V; Korean Society of Medical Biochemistry and Molecular Biology; 생화학분자생물학회
• Subjects: Adenoviridae - genetics; Adult; Animals; Biomedical and Life Sciences; Biomedicine; Calcineurin - metabolism; Calcineurin Inhibitors; Cells, Cultured; Chromatin Immunoprecipitation; Down Syndrome - metabolism; Down Syndrome - pathology; Fibroblasts - metabolism; Fibroblasts - pathology; Humans; Hydrogen Peroxide - pharmacology; Immunoglobulin G - immunology; Intracellular Signaling Peptides and Proteins - physiology; Male; Medical Biochemistry; Mice; Mice, Inbred ICR; Molecular Medicine; Muscle Proteins - physiology; Neuroblastoma - genetics; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurons - cytology; Neurons - metabolism; Original; Oxidants - pharmacology; Oxidative Stress; Peptide Fragments - immunology; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - pharmacology; Skin - pathology; Stem Cells; Young Adult; 생화학; fibroblasts; RCAN1 protein, human; hydrogen peroxide; DSCR1 protein, mouse; Down syndrome; calcineurin; oxidative stress
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2009.41.7.052

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. Convertsely, 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.