Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles.

J. Yang, B. Rothermel, R. B. Vega, N. Frey, T. A. McKinsey, E. N. Olson, R. Bassel-Duby, R. S. Williams

Research output: Contribution to journalArticle

269 Citations (Scopus)

Abstract

Calcineurin, a calcium/calmodulin-regulated protein phosphatase, modulates gene expression in cardiac and skeletal muscles during development and in remodeling responses such as cardiac hypertrophy that are evoked by environmental stresses or disease. Recently, we identified two genes encoding proteins (MCIP1 and MCIP2) that are enriched in striated muscles and that interact with calcineurin to inhibit its enzymatic activity. In the present study, we show that expression of MCIP1 is regulated by calcineurin activity in hearts of mice with cardiac hypertrophy, as well as in cultured skeletal myotubes. In contrast, expression of MCIP2 in the heart is not altered by activated calcineurin but responds to thyroid hormone, which has no effect on MCIP1. A approximately 900-bp intragenic segment located between exons 3 and 4 of the MCIP1 gene functions as an alternative promoter that responds to calcineurin. This region includes a dense cluster of 15 consensus binding sites for NF-AT transcription factors. Because MCIP proteins can inhibit calcineurin, these results suggest that MCIP1 participates in a negative feedback circuit to diminish potentially deleterious effects of unrestrained calcineurin activity in cardiac and skeletal myocytes. Inhibitory effects of MCIP2 on calcineurin activity may be pertinent to gene switching events driven by thyroid hormone in striated muscles. The full text of this article is available at http://www. circresaha.org.

Original languageEnglish (US)
JournalCirculation Research
Volume87
Issue number12
StatePublished - Dec 8 2000

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Striated Muscle
Calcineurin
Proteins
Skeletal Muscle Fibers
Cardiomegaly
Thyroid Hormones
NFATC Transcription Factors
Muscle Development
Phosphoprotein Phosphatases
Calmodulin
Cardiac Myocytes
Genes
Exons
Myocardium
Skeletal Muscle
Binding Sites
Calcium
Gene Expression

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. / Yang, J.; Rothermel, B.; Vega, R. B.; Frey, N.; McKinsey, T. A.; Olson, E. N.; Bassel-Duby, R.; Williams, R. S.

In: Circulation Research, Vol. 87, No. 12, 08.12.2000.

Research output: Contribution to journalArticle

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