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Inhibition of DUSP5 by class I HDACs requires activity of the ERK kinase, mitogen-activated protein kinase kinase (MEK), revealing a self-reinforcing mechanism for promotion of cardiac ERK signaling. In cardiac myocytes treated with highly selective class I HDAC inhibitors, nuclear ERK1\/2 signaling is suppressed in a manner that is absolutely dependent on DUSP5. In contrast, cytosolic ERK1\/2 activation is maintained under these same conditions. Ectopic expression of DUSP5 in cardiomyocytes results in potent inhibition of agonist-dependent hypertrophy through a mechanism involving suppression of the gene program for hypertrophic growth. These findings define unique roles for class I HDACs and DUSP5 as integral components of a regulatory signaling circuit that controls cardiac hypertrophy.<\/jats:p>","DOI":"10.1073\/pnas.1301509110","type":"journal-article","created":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T01:03:13Z","timestamp":1369875793000},"page":"9806-9811","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Signal-dependent repression of DUSP5 by class I HDACs controls nuclear ERK activity and cardiomyocyte hypertrophy"],"prefix":"10.1073","volume":"110","author":[{"given":"Bradley S.","family":"Ferguson","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO 80045;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke C.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO 80309;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Y.","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO 80045;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian G.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Wempe","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045;"},{"name":"University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO 80045; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence F.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Holson","sequence":"additional","affiliation":[{"name":"Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"McKinsey","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO 80045;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,5,29]]},"reference":[{"key":"e_1_3_3_1_2","first-page":"e2","article-title":"Heart disease and stroke statistics\u20142012 update: A report from the American Heart Association","volume":"125","author":"Roger VL","year":"2012","unstructured":"VL Roger, et al., Heart disease and stroke statistics\u20142012 update: A report from the American Heart Association. 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