GTAT4和Myocardin相互作用调控心肌肥厚

项目名称： GTAT4和Myocardin相互作用调控心肌肥厚

项目编号： No.31471282

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 邢卫兵

作者单位： 武汉科技大学

项目金额： 85万元

中文摘要： 蛋白质转录因子间相互作用为机体提供了更精细的转录调节，但也使转录调控更为复杂。Myocardin是血清反应因子（SRF）强力辅助转录因子，可激活心肌肥厚基因转录，诱发心肌肥厚。GATA结合蛋白4（GATA4）也可促发心肌肥厚。但二者共同作用时，GATA4却抑制Myocardin对心肌肥厚基因激活。在我们先前这些发现基础上，本研究将进一步在转基因整体动物水平上，证明其相互作用，并利用细胞分子生物学手段，阐明GATA4抑制Myocardin介导心肌肥厚机制。包括二者蛋白相互作用，降低myocardin与SRF结合,抑制心肌肥厚基因的转录；抑制Myocardin表达并使其磷酸化降低其活性；GATA4和Myocardin竞争性与p300结合,进而消弱了p300与Myocardin协同促发心肌肥厚基因的激活等。最终，在分子-细胞-整体水平，证明GATA4抑制Myocardin触发的心肌肥厚最新机制。

中文关键词： Myocardin；GATA4；转录调控；心肌肥厚

英文摘要： Interactions of different tanscriptional factors can provide precise transcriptional regulation in human physiology and pathophysiology, but make it to be more complex.Myocardin is poweful co-transcriptional factor of serum response factor(SRF) and can activate the related genes of cardiac hypertrophy to mediate cardiac hypertrophy in vitro. GATA binding protein 4 (GATA4) also can trigger cardiac hypertrophy. But when the two work together, GATA4 inhibits the activation of cardiac hypertrophy gene induced by Myocardin. Based on our these previous findings , this study will further prove their interactions in transgenic mouse. The mechanism of myocardin- mediated cardiac hypertrophy inhibited by GATA4 will be investigated with a variety of cellular and molecular biology methods, which GATA4 can reduce myocardin binding with SRF because of their protein - protein interaction, inhibit myocardin expression and enhance its phosphorylation to decrease its transactivation.GATA4 may also compete binding with p300 with myocardin and result in weakening the cardiac hypertrophy gene activation. Eventually, novel evidence will be provided to prove that GATA4 suppress the cardiac hypertrophy triggered by myocardin in vitro and in vivo.

英文关键词： Myocardin;GATA4;regulate transctivation;cardiac hypertrophy