Identification of a peptide fragment of DSCR1 that competitively inhibits calcineurin activity in vitro and in vivo

Autor: Garrett Greenan, Tom Ellenberger, Frank McKeon, Betty Liwah Chan
Rok vydání: 2005
Předmět:
Zdroj: Proceedings of the National Academy of Sciences. 102:13075-13080
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.0503846102
Popis: Calcineurin phosphatase activity regulates the nuclear localization of the nuclear factor of activated T cells (NFAT) family of transcription factors during immune challenge. Calcineurin inhibitors, such as the cyclosporin A–cyclophilin A and FK506–FKBP12 complexes, regulate this enzymatic activity noncompetitively by binding at a site distinct from the enzyme active site. A family of endogenous protein inhibitors of calcineurin was recently identified and shown to block calcineurin-mediated NFAT nuclear localization and transcriptional activation. One such inhibitor, Down Syndrome Critical Region 1 (DSCR1), functions in T cell activation, cardiac hypertrophy, and angiogenesis. We have identified a small region of DSCR1 that is a potent inhibitor of calcineurin activity in vitro and in vivo .
Databáze: OpenAIRE