title: [Functional Analysis of GATA4 Complex, a Cardiac Hypertrophy-response Transcriptional Factor, Using a Proteomics Approach].
abstract: Various stresses on the heart, such as myocardial infarction and hemodynamic overload, activate the sympathetic nervous system and the renin-angiotensin system, ultimately reach the nuclei of cardiomyocytes, and change the pattern of gene expression associated with cardiac hypertrophy. Although present pharmacological therapy for heart failure targets such extracellular molecules, mortality due to heart failure is still high. A zinc finger protein, GATA4, is one of the hypertrophy-responsive transcription factors, forms a functional protein complex with an intrinsic histone acetyltransferase, p300, and regulates pathological cardiac hypertrophy. Disruption of this complex results in the inhibition of cardiac hypertrophy and heart failure in vivo. To establish a more effective therapy for heart failure, we have been analyzing a common nuclear pathway within cardiomyocytes. We identified 73 GATA4 binding proteins by tandem-affinity purification and mass spectrometric analysis. Noble GATA4 binding partners, such as cyclin-dependent kinase-9 (Cdk9: the core factor of positive transcription elongation factor b) and retinoblastoma-association protein 48/46 (RbAp48/46: the co-repressor complexes containing HDAC1/2), regulate the p300/GATA4-mediated signaling pathway and hypertrophic responses. Further analysis of p300/GATA4 complex is expected to identify target molecules for heart failure therapy.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Shizuoka.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sunagawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Katanasaka
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Wada
authors.forename: Koji
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Morimoto
mesh_terms: D006332:Cardiomegaly / Q000188:drug therapy* / Q000235:genetics*; D042863:Cyclin-Dependent Kinase 9; D050991:GATA4 Transcription Factor / Q000302:isolation & purification / Q000502:physiology*; D051548:Histone Acetyltransferases; D006801:Humans; D058990:Molecular Targeted Therapy; D046912:Multiprotein Complexes; D011485:Protein Binding; D040901:Proteomics; D056505:Retinoblastoma-Binding Protein 4; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D042863:Cyclin-Dependent Kinase 9; D050991:GATA4 Transcription Factor; D051548:Histone Acetyltransferases; D046912:Multiprotein Complexes; D056505:Retinoblastoma-Binding Protein 4; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C484170:GATA4 protein, human; C082637:RBBP4 protein, human