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首页> 外文期刊>The European Journal of Neuroscience >The transcription factor CCAAT enhancer-binding protein β protects rat cerebellar granule neurons from apoptosis through its transcription-activating isoforms
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The transcription factor CCAAT enhancer-binding protein β protects rat cerebellar granule neurons from apoptosis through its transcription-activating isoforms

机译：转录因子CCAAT增强子结合蛋白β通过其转录激活亚型保护大鼠小脑颗粒神经元免于凋亡

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CCAAT enhancer-binding protein β is a transcription factor that is involved in many brain processes, although its role in neuronal survival/death remains unclear. By using primary cultures of rat cerebellar granule neurons, we have shown here that CCAAT enhancer-binding protein β is present as all of its isoforms: the transcriptional activators liver activator proteins 1 and 2, and the transcriptional inhibitor liver inhibitory protein. We have also shown that liver activator protein 1 undergoes post-translational modifications, such as phosphorylation and sumoylation. These isoforms have different subcellular localizations, liver activator protein 2 being found in the cytosolic fraction only, liver inhibitory protein in the nucleus only, and liver activator protein 1 in both fractions. Through neuronal apoptosis induction by shifting mature cerebellar granule neurons to low-potassium medium, we have demonstrated that nuclear liver activator protein 1 expression decreases and its phosphorylation disappears, whereas liver inhibitory protein levels increase in the nuclear fraction, suggesting a pro-survival role for liver activator protein transcriptional activation and a pro-apoptotic role for liver inhibitory protein transcriptional inhibition. To confirm this, we transfected cerebellar granule neurons with plasmids expressing liver activator protein 1, liver activator protein 2, or liver inhibitory protein respectively, and observed that both liver activator proteins, which increase CCAAT-dependent transcription, but not liver inhibitory protein, counteracted apoptosis, thus demonstrating the pro-survival role of liver activator proteins. These data significantly improve our current understanding of the role of CCAAT enhancer-binding protein β in neuronal survival/apoptosis.
机译：尽管CCAAT增强子结合蛋白β在神经元存活/死亡中的作用尚不清楚，但它是涉及许多大脑过程的转录因子。通过使用大鼠小脑颗粒神经元的原代培养物，我们在此处显示了CCAAT增强子结合蛋白β以其所有同工型形式存在：转录激活子肝激活蛋白1和2，以及转录抑制剂肝抑制蛋白。我们还表明，肝脏激活蛋白1经历了翻译后修饰，例如磷酸化和SUMO化。这些同工型具有不同的亚细胞定位，仅在胞质组分中发现了肝激活蛋白2，仅在细胞核中发现了肝抑制蛋白，在这两个组分中均发现了肝激活蛋白1。通过将成熟的小脑颗粒神经元转移至低钾培养基来诱导神经元凋亡，我们已证明核肝激活蛋白1的表达减少，其磷酸化消失，而肝抑制蛋白的水平在核级分中增加，表明该蛋白具有促生存作用。肝激活蛋白的转录激活和促凋亡作用对肝抑制蛋白的转录抑制作用。为了证实这一点，我们分别用表达肝激活蛋白1，肝激活蛋白2或肝抑制蛋白的质粒转染了小脑颗粒神经元，并观察到两种肝激活蛋白均增加了CCAAT依赖性转录，但不抑制肝抑制蛋白细胞凋亡，从而证明了肝激活蛋白的促生存作用。这些数据大大改善了我们目前对CCAAT增强子结合蛋白β在神经元存活/凋亡中的作用的了解。

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