RGD Reference Report - Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy. - Rat Genome Database

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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.
RGD ID: 734902
Pubmed: PMID:12515860   (View Abstract at PubMed)
PMCID: PMC141054   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0237225100   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PPP3CAHumanCardiomegaly  ISOPpp3ca (Mus musculus) RGD 
Ppp3caRatCardiomegaly  ISOPpp3ca (Mus musculus) RGD 
Ppp3caMouseCardiomegaly  IAGP  RGD 
RCAN1HumanCardiomegaly  ISORcan1 (Mus musculus) RGD 
Rcan1MouseCardiomegaly  IAGP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp3ca  (protein phosphatase 3 catalytic subunit alpha)

Genes (Mus musculus)
Ppp3ca  (protein phosphatase 3, catalytic subunit, alpha isoform)
Rcan1  (regulator of calcineurin 1)

Genes (Homo sapiens)
PPP3CA  (protein phosphatase 3 catalytic subunit alpha)
RCAN1  (regulator of calcineurin 1)

Objects referenced in this article
Gene Rcan2 regulator of calcineurin 2 Mus musculus

Additional Information