title: CIP4 is required for the hypertrophic growth of neonatal cardiac myocytes.
abstract: BACKGROUND
  CIP4 is a scaffold protein that regulates membrane deformation and tubulation, organization of the actin cytoskeleton, endocytosis of growth factor receptors, and vesicle trafficking. Although expressed in the heart, CIP4 has not been studied with regards to its potential function in cardiac myocytes.
  
  
  RESULTS
  We now show using RNA interference that CIP4 expression in neonatal rat ventricular myocytes is required for the induction of non-mitotic, hypertrophic growth by the α-adrenergic agonist phenylephrine, the IL-6 cytokine leukemia inhibitor factor, and fetal bovine serum, as assayed using morphometry, immunocytochemistry for the hypertrophic marker atrial natriuretic factor and [3H]leucine incorporation for de novo protein synthesis. This requirement was consistent with the induction of CIP4 expression by hypertrophic stimulation. The inhibition of myocyte hypertrophy by CIP4 small interfering oligonucleotides (siRNA) was rescued by expression of a recombinant CIP4 protein, but not by a mutant lacking the N-terminal FCH domain responsible for CIP4 intracellular localization.
  
  
  CONCLUSIONS
  These results imply that CIP4 plays a significant role in the intracellular hypertrophic signal transduction network that controls the growth of cardiac myocytes in heart disease.
authors.affiliation: Interdisciplinary Stem Cell Institute, Department of Pediatrics, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33101, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Rusconi
authors.forename: Hrishikesh
authors.initials: H
authors.lastname: Thakur
authors.forename: Jinliang
authors.initials: J
authors.lastname: Li
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kapiloff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D048429:Cell Size; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010656:Phenylephrine / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015850:Interleukin-6; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D034741:RNA, Small Interfering; C406285:TRIP10 protein, human; D010656:Phenylephrine
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