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论文类型：期刊论文

发表时间：2015-05-01

发表刊物：CELLULAR AND MOLECULAR LIFE SCIENCES

收录刊物：SCIE、Scopus

卷号：72

期号：10

页面范围：2005-2022

ISSN号：1420-682X

关键字：Cardiogenesis; Sarcomeric myosin heavy chain; Pluripotent mouse embryonal carcinoma cells; Signaling transduction; Gene regulation

摘要：The regulation of cardiac differentiation is critical for maintaining normal cardiac development and function. The precise mechanisms whereby cardiac differentiation is regulated remain uncertain. Here, we have identified a GATA-4 target, EGF, which is essential for cardiogenesis and regulates cardiac differentiation in a dose- and time-dependent manner. Moreover, EGF demonstrates functional interaction with GATA-4 in inducing the cardiac differentiation of P19CL6 cells in a time- and dose-dependent manner. Biochemically, GATA-4 forms a complex with STAT3 to bind to the EGF promoter in response to EGF stimulation and cooperatively activate the EGF promoter. Functionally, the cooperation during EGF activation results in the subsequent activation of cyclin D1 expression, which partly accounts for the lack of additional induction of cardiac differentiation by the GATA-4/STAT3 complex. Thus, we propose a model in which the regulatory cascade of cardiac differentiation involves GATA-4, EGF, and cyclin D1.