A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling

Beverly Rothermel, Rick B. Vega, John Yang, Hai Wu, Rhonda Bassel-Duby, R. Sanders Williams

Research output: Contribution to journalArticle

343 Scopus citations

Abstract

Here we describe a small family of proteins, termed MCIP1 and MCIP2 (for myocyte-enriched calcineurin interacting protein), that are expressed most abundantly in striated muscles and that form a physical complex with calcineurin A. MCIP1 is encoded by DSCR1, a gene located in the Down syndrome critical region. Expression of the MCIP family of proteins is up-regulated during muscle differentiation, and their forced overexpression inhibits calcineurin signaling to a muscle-specific target gene in a myocyte cell background. Binding of MCIP1 to calcineurin A requires sequence motifs that resemble calcineurin interacting domains found in NFAT proteins. The inhibitory action of MCIP1 involves a direct association with the catalytic domain of calcineurin, rather than interference with the function of downstream components of the calcineurin signaling pathway. The interaction between MCIP proteins and calcineurin may modulate calcineurin-dependent pathways that control hypertrophic growth and selective programs of gene expression in striated muscles.

Original languageEnglish (US)
Pages (from-to)8719-8725
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number12
DOIs
StatePublished - Mar 24 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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