The cyclic AMP response element in the Bcl-2 promoter confers inducibility by hypoxia in neuronal cells
The cyclic AMP response element in the Bcl-2 promoter confers inducibility by hypoxia in neuronal cells
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DOI：
10.1016/s0169-328x(01)00158-9
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发表时间：
2001-08-15
期刊：
影响因子：
--
通讯作者：
Latchman, DS
中科院分区：
文献类型：
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作者：
Freeland, K;Boxer, LM;Latchman, DS
在神经元细胞中，抗凋亡Bcl-2基因的表达由缺氧诱导并产生保护作用。我们在这里表明，这种效果是依赖于环磷酸腺苷反应元件（CRE）的Bcl-2启动子，因为该元件的突变废除的响应和分离的CRE可以赋予异源启动子的响应。然而，有趣的是，Bcl-2启动子中的CRE并不使启动子对环AMP有反应，并且对于其对神经生长因子的反应不是必需的。尽管缺乏环AMP反应性，Bcl-2启动子通过CRE响应缺氧的激活需要CREB转录因子，并且与CREB在丝氨酸133上的磷酸化增强和CREB结合蛋白CBP响应缺氧的转录激活增强相关。这一发现确立了CRE在缺氧诱导Bcl-2基因表达中的重要性，允许Bcl-2蛋白保护神经元细胞免受这种破坏性刺激。(C)2001 Elsevier Science BY保留所有权利。
In neuronal cells, expression of the anti-apoptotic Bcl-2 gene is induced by hypoxia and produces a protective effect. We show here that this effect is dependent upon the cyclic AMP response element (CRE) in the Bcl-2 promoter since mutation of this element abolishes the response and the isolated CRE can confer the response on a heterologous promoter. Interestingly however, the CRE in the Bcl-2 promoter does not render the promoter responsive to cyclic AMP and is not essential for its response to nerve growth factor. Despite the lack of cyclic AMP responsiveness, activation of the Bcl-2 promoter via the CRE in response to hypoxia requires the CREB transcription factor and is associated with the enhanced phosphorylation of CREB on serine 133 and enhanced transcriptional activation by the CREB-binding protein, CBP, in response to hypoxia. This finding establishes the importance of the CRE in the induction of Bcl-2 gene expression by hypoxia, allowing the Bcl-2 protein to protect neuronal cells against this damaging stimulus. (C) 2001 Elsevier Science BY All rights reserved.