HDAC‐3 Participates in the Repression of e2f‐Dependent Gene Transcription in Primary Differentiated Neurons
HDAC‐3 Participates in the Repression of e2f‐Dependent Gene Transcription in Primary Differentiated Neurons
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DOI：
10.1196/annals.1329.076
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发表时间：
2004-12
影响因子：
5.2
通讯作者：
I. Panteleeva;C. Rouaux;Y. Larmet;S. Boutillier;J. Loeffler;A. Boutillier
中科院分区：
文献类型：
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作者：
I. Panteleeva;C. Rouaux;Y. Larmet;S. Boutillier;J. Loeffler;A. Boutillier
摘要：e2f - 1基因表达的激活已经在许多神经元凋亡模型中得到证实。在患有不同神经退行性疾病的患者的死后大脑中也观察到积累的E2F‐1蛋白。我们之前在原代神经元培养中表明，在神经保护条件下，通过HDAC依赖性调节e2f - 1基因启动子中的e2f -应答元件（e2f - REs）， e2f - 1基因转录被积极抑制。在这里，我们通过凝胶位移分析进一步研究了与这些位点结合的蛋白质复合物。我们发现，与神经保护条件相比，E2F‐REs特异性结合蛋白在凋亡条件下发生改变，这表明该复合物的蛋白质成分可能在细胞凋亡发生时发生改变。事实上，Western blot分析显示Rb/E2F结合蛋白HDAC‐3在细胞凋亡过程中存在时间依赖性降解，这种降解是caspase依赖性的。总之，这些数据表明HDAC‐3是参与神经保护所必需的主动e2f‐1抑制的良好候选者。
Abstract: Activation of e2f‐1 gene expression is an event that has been now established in many models of neuronal apoptosis. Accumulated E2F‐1 protein has also been observed in post mortem brains obtained from patients suffering from different neurodegenerative diseases. We have previously shown in primary neuronal cultures that e2f‐1 gene transcription was actively repressed in neuroprotective conditions through HDAC‐dependent regulation on the E2F‐responsive elements (E2F‐REs) located in the e2f‐1 gene promoter. Here, we further investigated the protein complex bound to these sites by gel shift analysis. We found that the specific protein binding to E2F‐REs is altered in apoptotic conditions compared to neuroprotective conditions, suggesting that the proteic constituents of the complex are likely to be modified upon apoptosis onset. Indeed, Western blot analysis showed a time‐dependent degradation of the Rb/E2F binding protein HDAC‐3 during apoptosis, a degradation that is caspase‐dependent. Altogether, these data point to HDAC‐3 as a good candidate involved in the active e2f‐1 repression necessary for neuroprotection.