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.
journal_name
Circ Resjournal_title
Circulation researchauthors
Yang J,Rothermel B,Vega RB,Frey N,McKinsey TA,Olson EN,Bassel-Duby R,Williams RSdoi
10.1161/01.res.87.12.e61subject
Has Abstractpub_date
2000-12-08 00:00:00pages
E61-8issue
12eissn
0009-7330issn
1524-4571journal_volume
87pub_type
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更新日期:1987-08-01 00:00:00
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更新日期:2018-05-25 00:00:00
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更新日期:1981-09-01 00:00:00
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更新日期:2004-02-20 00:00:00
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更新日期:2016-04-29 00:00:00
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更新日期:1991-10-01 00:00:00
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更新日期:1986-09-01 00:00:00
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更新日期:2011-08-05 00:00:00
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更新日期:2009-04-10 00:00:00
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更新日期:2014-02-14 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.115.307872
更新日期:2016-02-05 00:00:00
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更新日期:2014-01-17 00:00:00