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

Publication ,  Journal Article
Yang, J; Rothermel, B; Vega, RB; Frey, N; McKinsey, TA; Olson, EN; Bassel-Duby, R; Williams, RS
Published in: Circ Res
December 8, 2000

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.

Duke Scholars

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

December 8, 2000

Volume

87

Issue

12

Start / End Page

E61 / E68

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Thyroid Hormones
  • Signal Transduction
  • RNA, Messenger
  • Proteins
  • Muscle, Skeletal
  • Muscle Proteins
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Yang, J., Rothermel, B., Vega, R. B., Frey, N., McKinsey, T. A., Olson, E. N., … Williams, R. S. (2000). Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Circ Res, 87(12), E61–E68. https://doi.org/10.1161/01.res.87.12.e61
Yang, J., B. Rothermel, R. B. Vega, N. Frey, T. A. McKinsey, E. N. Olson, R. Bassel-Duby, and R. S. Williams. “Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles.Circ Res 87, no. 12 (December 8, 2000): E61–68. https://doi.org/10.1161/01.res.87.12.e61.
Yang J, Rothermel B, Vega RB, Frey N, McKinsey TA, Olson EN, et al. Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Circ Res. 2000 Dec 8;87(12):E61–8.
Yang, J., et al. “Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles.Circ Res, vol. 87, no. 12, Dec. 2000, pp. E61–68. Pubmed, doi:10.1161/01.res.87.12.e61.
Yang J, Rothermel B, Vega RB, Frey N, McKinsey TA, Olson EN, Bassel-Duby R, Williams RS. Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Circ Res. 2000 Dec 8;87(12):E61–E68.

Published In

Circ Res

DOI

EISSN

1524-4571

Publication Date

December 8, 2000

Volume

87

Issue

12

Start / End Page

E61 / E68

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Thyroid Hormones
  • Signal Transduction
  • RNA, Messenger
  • Proteins
  • Muscle, Skeletal
  • Muscle Proteins
  • Mice, Inbred C57BL
  • Mice