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Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction

Item Type:Article
Title:Loss of muscle-specific RING-finger 3 predisposes the heart to cardiac rupture after myocardial infarction
Creators Name:Fielitz, J. and van Rooij, E. and Spencer, J.A. and Shelton, J.M. and Latif, S. and van der Nagel, R. and Bezprozvannaya, S. and de Windt, L. and Richardson, J.A. and Bassel-Duby, R. and Olson, E.N.
Abstract:RING-finger proteins commonly function as ubiquitin ligases that mediate protein degradation by the ubiquitin-proteasome pathway. Muscle-specific RING-finger (MuRF) proteins are striated muscle-restricted components of the sarcomere that are thought to possess ubiquitin ligase activity. We show that mice lacking MuRF3 display normal cardiac function but are prone to cardiac rupture after acute myocardial infarction. Cardiac rupture is preceded by left ventricular dilation and a severe decrease in cardiac contractility accompanied by myocyte degeneration. Yeast two-hybrid assays revealed four-and-a-half LIM domain (FHL2) and gamma-filamin proteins as MuRF3 interaction partners, and biochemical analyses showed these proteins to be targets for degradation by MuRF3. Accordingly, FHL2 and gamma-filamin accumulated to abnormal levels in the hearts of mice lacking MuRF3. These findings reveal an important role of MuRF3 in maintaining cardiac integrity and function after acute myocardial infarction and suggest that turnover of FHL2 and gamma-filamin contributes to this cardioprotective function of MuRF3.
Keywords:Heart failure, Cardiac stress response, Protein degradation, Sarcomere, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:104
Number:11
Page Range:4377-4382
Date:13 March 2007
Official Publication:https://doi.org/10.1073/pnas.0611726104
PubMed:View item in PubMed

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