Work

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

Year: 2005

Type: article

Abstract: 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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0503846102

Authors: Betty Chan, Garrett Greenan, Frank McKeon, Tom Ellenberger

Institution: Harvard University

Language: English

Topic: Signaling Pathways in Disease

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institutes of Health