Functional Analysis of GATA4 Complex, a Cardiac Hypertrophy-response Transcriptional Factor, Using a Proteomics Approach

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  • Sunagawa Yoichi
    Graduate School of Pharmaceutical Sciences, University of Shizuoka Kyoto Medical Center Shizuoka General Hospital
  • Katanasaka Yasufumi
    Graduate School of Pharmaceutical Sciences, University of Shizuoka Kyoto Medical Center Shizuoka General Hospital
  • Wada Hiromichi
    Kyoto Medical Center
  • Hasegawa Koji
    Kyoto Medical Center
  • Morimoto Tatsuya
    Graduate School of Pharmaceutical Sciences, University of Shizuoka Kyoto Medical Center Shizuoka General Hospital

Bibliographic Information

Other Title
  • プロテオミクスを基としたGATA4転写因子及び心肥大発症メカニズム解析
  • Symposium Review プロテオミクスを基としたGATA4転写因子及び心肥大発症メカニズム解析
  • Symposium Review プロテオミクス オ モト ト シタ GATA4 テンシャ インシ オヨビ シン ヒダイ ハッショウ メカニズム カイセキ

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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.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 136 (2), 151-156, 2016-02-01

    The Pharmaceutical Society of Japan

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