Transformation of eEF1Bδ into heat-shock response transcription factor by alternative splicing
Transformation of eEF1Bδ into heat-shock response transcription factor by alternative splicing
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DOI：
10.1038/embor.2011.82
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发表时间：
2011-07-01
期刊：
影响因子：
7.7
通讯作者：
Matsushita, Masayuki
中科院分区：
文献类型：
--
作者：
Kaitsuka, Taku;Tomizawa, Kazuhito;Matsushita, Masayuki
蛋白质翻译因子在各种应激反应中发挥着至关重要的作用。在这里，我们证明真核延伸因子 1B delta (eEF1B delta) 通过选择性剪接将其结构和功能从翻译因子转变为热休克反应转录因子。 eEF1B delta (eEF1B delta L) 的长亚型位于细胞核中，并与热休克转录因子 1 (HSF1) 配合诱导含有热休克元件 (HSE) 的基因。此外，eEF1BdL 的氨基末端结构域与 NF-E2 相关因子 2 (Nrf2) 结合并诱导应激反应血红素加氧酶 1 (HO1)。使用小干扰 RNA 特异性抑制 eEF1B delta L 可完全抑制 Nrf2 依赖性 HO1 诱导。此外，eEF1B delta L 在体外直接与 HSE 寡 DNA 结合，并在体内与 HO1 启动子区域中的 HSE 共有序列相关联。因此，eEF1B delta L 的转录作用可以为应激反应的分子机制提供新的见解。
Protein translation factors have crucial roles in a variety of stress responses. Here, we show that eukaryotic elongation factor 1B delta (eEF1B delta) changes its structure and function from a translation factor into a heat-shock response transcription factor by alternative splicing. The long isoform of eEF1B delta (eEF1B delta L) is localized in the nucleus and induces heat-shock element (HSE)-containing genes in cooperation with heat-shock transcription factor 1 (HSF1). Moreover, the amino-terminal domain of eEF1BdL binds to NF-E2-related factor 2 (Nrf2) and induces stress response haem oxygenase 1 (HO1). Specific inhibition of eEF1B delta L with small-interfering RNA completely inhibits Nrf2-dependent HO1 induction. In addition, eEF1B delta L directly binds to HSE oligo DNA in vitro and associates with the HSE consensus in the HO1 promoter region in vivo. Thus, the transcriptional role of eEF1B delta L could provide new insights into the molecular mechanism of stress responses.