{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T04:14:20Z","timestamp":1771906460717,"version":"3.50.1"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T00:00:00Z","timestamp":1340064000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0036799","type":"journal-article","created":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T17:07:45Z","timestamp":1340125665000},"page":"e36799","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["MEK1 Inhibits Cardiac PPAR\u03b1 Activity by Direct Interaction and Prevents Its Nuclear Localization"],"prefix":"10.1371","volume":"7","author":[{"given":"Hamid","family":"el Azzouzi","sequence":"first","affiliation":[]},{"given":"Stefanos","family":"Leptidis","sequence":"additional","affiliation":[]},{"given":"Meriem","family":"Bourajjaj","sequence":"additional","affiliation":[]},{"given":"Marc","family":"van Bilsen","sequence":"additional","affiliation":[]},{"given":"Paula A.","family":"da Costa Martins","sequence":"additional","affiliation":[]},{"given":"Leon J.","family":"De Windt","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2012,6,19]]},"reference":[{"key":"ref1","first-page":"S14","article-title":"Pathophysiology of congestive heart failure.","volume":"4","author":"GS Francis","year":"2003","journal-title":"Rev Cardiovasc Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/1074-5521(95)90045-4","article-title":"Peroxisome proliferator activated receptors: transcriptional regulators of adipogenesis, lipid metabolism and more.","volume":"2","author":"W Wahli","year":"1995","journal-title":"Chem Biol"},{"key":"ref3","first-page":"3930","article-title":"Nuclear receptors PPARbeta\/delta and PPARalpha direct distinct metabolic regulatory programs in the mouse heart.","volume":"117","author":"EM Burkart","year":"2007","journal-title":"J Clin Invest"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1006\/jmcc.2002.2061","article-title":"Peroxisome proliferator-activated receptor alpha (PPARalpha) signaling in the gene regulatory control of energy metabolism in the normal and diseased heart.","volume":"34","author":"BN Finck","year":"2002","journal-title":"J Mol Cell Cardiol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"H1571","DOI":"10.1152\/ajpheart.01340.2007","article-title":"Alterations in carbohydrate metabolism and its regulation in PPARalpha null mouse hearts.","volume":"294","author":"R Gelinas","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1161\/01.CIR.94.11.2837","article-title":"Fatty acid oxidation enzyme gene expression is downregulated in the failing heart.","volume":"94","author":"MN Sack","year":"1996","journal-title":"Circulation"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"6438","DOI":"10.1073\/pnas.94.12.6438","article-title":"A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program.","volume":"94","author":"MN Sack","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"4499","DOI":"10.1210\/endo.137.10.8828512","article-title":"The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin.","volume":"137","author":"A Shalev","year":"1996","journal-title":"Endocrinology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1210\/mend.14.12.0575","article-title":"Activation of peroxisome proliferator-activated receptors (PPARs) by their ligands and protein kinase A activators.","volume":"14","author":"G Lazennec","year":"2000","journal-title":"Mol Endocrinol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1161\/01.RES.84.6.633","article-title":"Signaling in myocardial hypertrophy: life after calcineurin?","volume":"84","author":"PH Sugden","year":"1999","journal-title":"Circ Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"44495","DOI":"10.1074\/jbc.M105945200","article-title":"p38 mitogen-activated protein kinase activates peroxisome proliferator-activated receptor alpha: a potential role in the cardiac metabolic stress response.","volume":"276","author":"PM Barger","year":"2001","journal-title":"J Biol Chem"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1128\/MCB.00601-06","article-title":"Interaction with MEK causes nuclear export and downregulation of peroxisome proliferator-activated receptor gamma.","volume":"27","author":"E Burgermeister","year":"2007","journal-title":"Mol Cell Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"6341","DOI":"10.1093\/emboj\/19.23.6341","article-title":"The MEK1-ERK1\/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice.","volume":"19","author":"OF Bueno","year":"2000","journal-title":"Embo J"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.4161\/cc.6.13.4453","article-title":"MAPK kinases as nucleo-cytoplasmic shuttles for PPARgamma.","volume":"6","author":"E Burgermeister","year":"2007","journal-title":"Cell Cycle"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/cvr\/cvn001","article-title":"Cardiac hypertrophy is enhanced in PPAR alpha\u2212\/\u2212 mice in response to chronic pressure overload.","volume":"78","author":"PJ Smeets","year":"2008","journal-title":"Cardiovasc Res"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1161\/01.CIR.0000127126.73759.23","article-title":"MEK1-ERK2 signaling pathway protects myocardium from ischemic injury in vivo.","volume":"109","author":"DJ Lips","year":"2004","journal-title":"Circulation"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cardiores.2005.04.012","article-title":"Myocyte apoptosis in heart failure.","volume":"67","author":"VP van Empel","year":"2005","journal-title":"Cardiovasc Res"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"15927","DOI":"10.1074\/jbc.M213102200","article-title":"Conditional expression of SV40 T-antigen in mouse cardiomyocytes facilitates an inducible switch from proliferation to differentiation.","volume":"278","author":"DW Rybkin, II, Markham","year":"2003","journal-title":"J Biol Chem"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"35152","DOI":"10.1074\/jbc.274.49.35152","article-title":"Characterization of the amino-terminal activation domain of peroxisome proliferator-activated receptor alpha. Importance of alpha-helical structure in the transactivating function.","volume":"274","author":"R Hi","year":"1999","journal-title":"J Biol Chem"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1080\/07391102.2003.10506879","article-title":"Comparative analysis of docking motifs in MAP-kinases and nuclear receptors.","volume":"20","author":"E Burgermeister","year":"2003","journal-title":"J Biomol Struct Dyn"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0002-9440(10)63737-6","article-title":"Activation of peroxisome proliferator-activated receptor-gamma reverses squamous metaplasia and induces transitional differentiation in normal human urothelial cells.","volume":"164","author":"CL Varley","year":"2004","journal-title":"Am J Pathol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1152\/japplphysiol.00392.2005","article-title":"Activation pattern of MAPK signaling in the hearts of trained and untrained rats following a single bout of exercise.","volume":"101","author":"M Iemitsu","year":"2006","journal-title":"J Appl Physiol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1152\/physiolgenomics.90296.2008","article-title":"Transcriptomic analysis of PPARalpha-dependent alterations during cardiac hypertrophy.","volume":"36","author":"PJ Smeets","year":"2008","journal-title":"Physiol Genomics"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.bbalip.2007.04.018","article-title":"Modulation of PPAR activity via phosphorylation.","volume":"1771","author":"KA Burns","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1242\/dev.02168","article-title":"MAP kinase subcellular localization controls both pattern and proliferation in the developing Drosophila wing.","volume":"133","author":"DR Marenda","year":"2006","journal-title":"Development"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"6168","DOI":"10.1074\/jbc.274.10.6168","article-title":"Nuclear localization of mitogen-activated protein kinase kinase 1 (MKK1) is promoted by serum stimulation and G2-M progression. Requirement for phosphorylation at the activation lip and signaling downstream of MKK.","volume":"274","author":"NS Tolwinski","year":"1999","journal-title":"J Biol Chem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1006\/jmcc.2001.1427","article-title":"Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch.","volume":"33","author":"Y Takeishi","year":"2001","journal-title":"J Mol Cell Cardiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.biocel.2006.09.002","article-title":"Gene expression profiling reveals complex changes following MEK-EE expression in cardiac myocytes.","volume":"39","author":"B Badrian","year":"2007","journal-title":"Int J Biochem Cell Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1161\/CIRCULATIONAHA.105.534594","article-title":"Decreased contractile and metabolic reserve in peroxisome proliferator-activated receptor-alpha-null hearts can be rescued by increasing glucose transport and utilization.","volume":"112","author":"I Luptak","year":"2005","journal-title":"Circulation"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1440-1681.2002.03655.x","article-title":"Transcriptional activation of energy metabolic switches in the developing and hypertrophied heart.","volume":"29","author":"JJ Lehman","year":"2002","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1172\/JCI9056","article-title":"Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth.","volume":"105","author":"PM Barger","year":"2000","journal-title":"J Clin Invest"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"22295","DOI":"10.1074\/jbc.M801296200","article-title":"NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure.","volume":"283","author":"M Bourajjaj","year":"2008","journal-title":"J Biol Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nm1272","article-title":"The transcriptional repressor Nab1 is a specific regulator of pathological cardiac hypertrophy.","volume":"11","author":"M Buitrago","year":"2005","journal-title":"Nat Med"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"29004","DOI":"10.1074\/jbc.M801297200","article-title":"Cooperative synergy between NFAT and MyoD regulates myogenin expression and myogenesis.","volume":"283","author":"AS Armand","year":"2008","journal-title":"J Biol Chem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1161\/CIRCULATIONAHA.105.608968","article-title":"MEF2 activates a genetic program promoting chamber dilation and contractile dysfunction in calcineurin-induced heart failure.","volume":"114","author":"RJ van Oort","year":"2006","journal-title":"Circulation"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cardiores.2007.04.026","article-title":"Activation of PPARdelta inhibits cardiac fibroblast proliferation and the transdifferentiation into myofibroblasts.","volume":"75","author":"BE Teunissen","year":"2007","journal-title":"Cardiovasc Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1038\/nsb836","article-title":"DNA binding is required for the apoptogenic action of apoptosis inducing factor.","volume":"9","author":"H Ye","year":"2002","journal-title":"Nat Struct Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"48617","DOI":"10.1074\/jbc.M206532200","article-title":"Requirement of nuclear factor of activated T-cells in calcineurin-mediated cardiomyocyte hypertrophy.","volume":"277","author":"E van Rooij","year":"2002","journal-title":"J Biol Chem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1161\/CIRCULATIONAHA.108.769984","article-title":"Conditional dicer gene deletion in the postnatal myocardium provokes spontaneous cardiac remodeling.","volume":"118","author":"PA da Costa Martins","year":"2008","journal-title":"Circulation"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.jacc.2006.02.075","article-title":"EUK-8, a superoxide dismutase and catalase mimetic, reduces cardiac oxidative stress and ameliorates pressure overload-induced heart failure in the harlequin mouse mutant.","volume":"48","author":"VP van Empel","year":"2006","journal-title":"J Am Coll Cardiol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0036799","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T02:59:17Z","timestamp":1540349957000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0036799"}},"subtitle":[],"editor":[{"given":"Annarosa","family":"Leri","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2012,6,19]]},"references-count":40,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2012,6,19]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0036799","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,6,19]]}}}