Exp Mol Med.  2009 Jul;41(7):471-477. 10.3858/emm.2009.41.7.052.

Down syndrome critical region 1 enhances the proteolytic cleavage of calcineurin

• Lee JE
• Jang H
• Cho EJ
• Youn HD

• KMID: 1058021
• DOI: http://doi.org/10.3858/emm.2009.41.7.052

Abstract

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.

Keyword

calcineurin; Down syndrome; DSCR1 protein, mouse; fibroblasts; hydrogen peroxide; oxidative stress; RCAN1 protein, human

MeSH Terms

Adenoviridae/genetics
Adult
Animals
Calcineurin/antagonists & inhibitors/*metabolism
Cells, Cultured
Chromatin Immunoprecipitation
Down Syndrome/*metabolism/pathology
Fibroblasts/metabolism/pathology
Humans
Hydrogen Peroxide/pharmacology
Immunoglobulin G/immunology
Intracellular Signaling Peptides and Proteins/*physiology
Male
Mice
Mice, Inbred ICR
Muscle Proteins/*physiology
Neuroblastoma/genetics/metabolism/pathology
Neurons/cytology/metabolism
Oxidants/pharmacology
Oxidative Stress
Peptide Fragments/immunology
RNA, Messenger/genetics/metabolism
RNA, Small Interfering/pharmacology
Rabbits
Reverse Transcriptase Polymerase Chain Reaction
Skin/pathology
Young Adult