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Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy.

Authors: Vega, RB  Rothermel, BA  Weinheimer, CJ  Kovacs, A  Naseem, RH  Bassel-Duby, R  Williams, RS  Olson, EN 
Citation: Vega RB, etal., Proc Natl Acad Sci U S A 2003 Jan 21;100(2):669-74. Epub 2003 Jan 6.
Pubmed: (View Article at PubMed) PMID:12515860
DOI: Full-text: DOI:10.1073/pnas.0237225100

The calcium/calmodulin-dependent protein phosphatase calcineurin stimulates cardiac hypertrophy in response to numerous stimuli. Calcineurin activity is suppressed by association with modulatory calcineurin-interacting protein (MCIP)1DSCR1, which is up-regulated by calcineurin signaling and has been proposed to function in a negative feedback loop to modulate calcineurin activity. To investigate the involvement of MCIP1 in cardiac hypertrophy in vivo, we generated MCIP1 null mice and subjected them to a variety of stress stimuli that induce cardiac hypertrophy. In the absence of stress, MCIP1(-/-) animals exhibited no overt phenotype. However, the lack of MCIP1 exacerbated the hypertrophic response to activated calcineurin expressed from a muscle-specific transgene, consistent with a role of MCIP1 as a negative regulator of calcineurin signaling. Paradoxically, however, cardiac hypertrophy in response to pressure overload or chronic adrenergic stimulation was blunted in MCIP1(-/-) mice. These findings suggest that MCIP1 can facilitate or suppress cardiac calcineurin signaling depending on the nature of the hypertrophic stimulus. These opposing roles of MCIP have important implications for therapeutic strategies to regulate cardiac hypertrophy through modulation of calcineurin-MCIP activity.

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CRRD Object Information
CRRD ID: 734902
Created: 2004-02-03
Species: All species
Last Modified: 2004-02-03
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.