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

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.

SUBMITTER: Chan B

PROVIDER: S-EPMC1201586 | biostudies-literature | 2005 Sep

REPOSITORIES: biostudies-literature

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

Chan Betty B Greenan Garrett G McKeon Frank F Ellenberger Tom T

Proceedings of the National Academy of Sciences of the United States of America 20050830 37

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 NFA ...[more]

PMID: 16131541

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