TY - JOUR
T1 - A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling
AU - Rothermel, Beverly
AU - Vega, Rick B.
AU - Yang, John
AU - Wu, Hai
AU - Bassel-Duby, Rhonda
AU - Williams, R. Sanders
PY - 2000/3/24
Y1 - 2000/3/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034708825&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034708825&partnerID=8YFLogxK
U2 - 10.1074/jbc.275.12.8719
DO - 10.1074/jbc.275.12.8719
M3 - Article
C2 - 10722714
AN - SCOPUS:0034708825
SN - 0021-9258
VL - 275
SP - 8719
EP - 8725
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 12
ER -