A Protein Encoded within the Down Syndrome Critical Region Is Enriched in Striated Muscles and Inhibits Calcineurin Signaling

• Published in: The Journal of biological chemistry Vol. 275; no. 12; pp. 8719 - 8725
• Main Authors: Rothermel, Beverly, Vega, Rick B., Yang, John, Wu, Hai, Bassel-Duby, Rhonda, Williams, R.Sanders
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.03.2000; American Society for Biochemistry and Molecular Biology
• Subjects: Alternative Splicing; Animals; calcineurin A; Calcineurin Inhibitors; Catalytic Domain; Cell Compartmentation; DNA-Binding Proteins - metabolism; Down Syndrome - genetics; DSCR1 gene; Humans; Intracellular Signaling Peptides and Proteins; Ionophores - pharmacology; MCIP1 protein; MCIP2 protein; MEF2 Transcription Factors; Mice; Multigene Family; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Myogenic Regulatory Factors; Protein Binding; Proteins; Signal Transduction; Tetradecanoylphorbol Acetate - pharmacology; Transcription Factors - metabolism; Transcriptional Activation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.275.12.8719

Here we describe a small family of proteins, termed MCIP1 and MCIP2 (for myocyte-enrichedcalcineurin interacting protein), that are expressed most abundantly in striated muscles and that form a physical complex with calcineurin A. MCIP1 is encoded byDSCR1, 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.