CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors
CREB-dependent Nur77 induction following depolarization in PC12 cells and neurons is modulated by MEF2 transcription factors
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DOI：
10.1111/j.1471-4159.2009.06521.x
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发表时间：
2010-02-01
影响因子：
4.7
通讯作者：
Chawla, Sangeeta
中科院分区：
文献类型：
--
作者：
Lam, Brian Yee Hong;Zhang, Wenting;Chawla, Sangeeta
核孤儿受体基因Nur77在神经细胞中的表达是由细胞内钙离子活性依赖性增加所诱导的。Nur77基因的钙敏感性被归因于招募转录因子cAMP反应元件结合蛋白(CREB)和肌细胞增强因子-2(MEF2)的两个不同的DNA调节区。在这里，我们使用CREB和MEF2蛋白的显性干扰和成分活性突变来评估它们在未分化的PC12细胞和海马神经元中对去极化诱导的Nur77表达的相对贡献。我们证明，虽然CREB是钙激活的Nur77表达所必需的，但MEF2通过在静止细胞中作为抑制物来调节CREB依赖的Nur77的表达。
Expression of the nuclear orphan receptor gene Nur77 in neuronal cells is induced by activity-dependent increases in intracellular Ca2+ ions. Ca2+ responsiveness of the Nur77 gene has been attributed to two distinct DNA regulatory regions that recruit the transcription factors cAMP response element binding protein (CREB) and myocyte enhancer factor-2 (MEF2). Here we used dominant interfering and constitutively active mutants of CREB and MEF2 proteins to assess their relative contribution to depolarization-induced Nur77 expression in undifferentiated PC12 cells and hippocampal neurons. We show that while CREB is necessary for Ca2+-activated Nur77 expression MEF2 functions to modulate CREB-dependent Nur77 expression by acting as a repressor in quiescent cells.