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

Publication ,  Journal Article
Vega, RB; Rothermel, BA; Weinheimer, CJ; Kovacs, A; Naseem, RH; Bassel-Duby, R; Williams, RS; Olson, EN
Published in: Proc Natl Acad Sci U S A
January 21, 2003

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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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 21, 2003

Volume

100

Issue

2

Start / End Page

669 / 674

Location

United States

Related Subject Headings

  • Muscle Proteins
  • Mice, Knockout
  • Mice
  • Male
  • Intracellular Signaling Peptides and Proteins
  • DNA-Binding Proteins
  • Cardiomegaly
  • Calcineurin
  • Animals
 

Citation

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Vega, R. B., Rothermel, B. A., Weinheimer, C. J., Kovacs, A., Naseem, R. H., Bassel-Duby, R., … Olson, E. N. (2003). Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy. Proc Natl Acad Sci U S A, 100(2), 669–674. https://doi.org/10.1073/pnas.0237225100
Vega, Rick B., Beverly A. Rothermel, Carla J. Weinheimer, Atilla Kovacs, R. H. Naseem, Rhonda Bassel-Duby, R. S. Williams, and Eric N. Olson. “Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy.Proc Natl Acad Sci U S A 100, no. 2 (January 21, 2003): 669–74. https://doi.org/10.1073/pnas.0237225100.
Vega RB, Rothermel BA, Weinheimer CJ, Kovacs A, Naseem RH, Bassel-Duby R, et al. Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):669–74.
Vega, Rick B., et al. “Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy.Proc Natl Acad Sci U S A, vol. 100, no. 2, Jan. 2003, pp. 669–74. Pubmed, doi:10.1073/pnas.0237225100.
Vega RB, Rothermel BA, Weinheimer CJ, Kovacs A, Naseem RH, Bassel-Duby R, Williams RS, Olson EN. Dual roles of modulatory calcineurin-interacting protein 1 in cardiac hypertrophy. Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):669–674.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

January 21, 2003

Volume

100

Issue

2

Start / End Page

669 / 674

Location

United States

Related Subject Headings

  • Muscle Proteins
  • Mice, Knockout
  • Mice
  • Male
  • Intracellular Signaling Peptides and Proteins
  • DNA-Binding Proteins
  • Cardiomegaly
  • Calcineurin
  • Animals