The membrane-associated transcription factor NAC089 controls ER-stress-induced programmed cell death in plants.

The membrane-associated transcription factor NAC089 controls ER-stress-induced programmed cell death in plants.
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DOI:
10.1371/journal.pgen.1004243
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发表时间:
2014-03
期刊:
影响因子:
4.5
通讯作者:
Liu JX
Liu JX
中科院分区:
生物学2区
文献类型:
--
作者:
Yang ZT;Wang MJ;Sun L;Lu SJ;Bi DL;Sun L;Song ZT;Zhang SS;Zhou SF;Liu JX

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未折叠蛋白反应(UPR)被激活,通过减少内质网(ER)中错误折叠蛋白的积累来维持细胞存活。当ER胁迫严重时,UPR也促进程序性细胞死亡(PCD);然而,其潜在的分子机制知之甚少,特别是在植物中。以前,两个膜相关的转录因子(MTF),bZIP 28和bZIP 60,被确定为在植物内质网应激反应中细胞存活的关键调节因子。在这里,我们报告的另一个MTF,NAC 089,作为一个重要的PCD调节拟南芥(拟南芥)植物的鉴定。在ER应激条件下,NAC 089从ER膜重新定位到核。NAC 089的截短形式的诱导表达,其中跨膜结构域被删除,诱导PCD增加半胱天冬酶3/7样活性和DNA片段化。敲低拟南芥中的NAC 089赋予ER胁迫耐受性并损害ER胁迫诱导的caspase样活性。转录调控分析和ChIP-qPCR结果表明,NAC 089在调控下游PCD相关基因如NAC 094、MC 5和BAG 6中发挥重要作用。此外,NAC 089通过ER应激上调,ER应激直接由bZIP 28和bZIP 60控制。这些结果表明,NAC 089的核移位促进ER胁迫诱导的PCD,并且bZIP 28和bZIP 60在植物ER胁迫响应期间引发促存活和促死亡信号。蛋白质折叠对于真核生物的发育和对环境胁迫的反应至关重要。当过量的错误折叠蛋白在内质网(ER)中积累时,未折叠蛋白反应(UPR)被触发以通过优化蛋白质折叠来促进细胞存活,并且当应激严重时也促进程序性细胞死亡(PCD)。然而,ER应力感知与PCD的联系在很大程度上是未知的。在这里,我们报告的一个膜相关转录因子NAC 089作为一个重要的调节ER应力诱导的PCD在植物中的鉴定。我们已经建立了一个以前未被认识的ER压力传感器和PCD调节分子之间的联系。我们已经表明,细胞器到细胞器易位的转录因子是重要的,它的功能在转录调控。我们的研究结果提供了新的见解PCD在植物中,特别是在ER胁迫条件下的分子机制。
The unfolded protein response (UPR) is activated to sustain cell survival by reducing misfolded protein accumulation in the endoplasmic reticulum (ER). The UPR also promotes programmed cell death (PCD) when the ER stress is severe; however, the underlying molecular mechanisms are less understood, especially in plants. Previously, two membrane-associated transcriptions factors (MTFs), bZIP28 and bZIP60, were identified as the key regulators for cell survival in the plant ER stress response. Here, we report the identification of another MTF, NAC089, as an important PCD regulator in Arabidopsis (Arabidopsis thaliana) plants. NAC089 relocates from the ER membrane to the nucleus under ER stress conditions. Inducible expression of a truncated form of NAC089, in which the transmembrane domain is deleted, induces PCD with increased caspase 3/7-like activity and DNA fragmentation. Knock-down NAC089 in Arabidopsis confers ER stress tolerance and impairs ER-stress-induced caspase-like activity. Transcriptional regulation analysis and ChIP-qPCR reveal that NAC089 plays important role in regulating downstream genes involved in PCD, such as NAC094, MC5 and BAG6. Furthermore, NAC089 is up-regulated by ER stress, which is directly controlled by bZIP28 and bZIP60. These results show that nuclear relocation of NAC089 promotes ER-stress-induced PCD, and both pro-survival and pro-death signals are elicited by bZIP28 and bZIP60 during plant ER stress response. Protein folding is fundamentally important for development and responses to environmental stresses in eukaryotes. When excess misfolded proteins are accumulated in the endoplasmic reticulum (ER), the unfolded protein response (UPR) is triggered to promote cell survival through optimizing protein folding, and also promote programmed cell death (PCD) when the stress is severe. However, the link from ER-stress-sensing to PCD is largely unknown. Here, we report the identification of one membrane-associated transcription factor NAC089 as an important regulator of ER stress-induced PCD in plants. We have established a previously unrecognized molecular connection between ER stress sensors and PCD regulators. We have shown that organelle-to-organelle translocation of a transcription factor is important for its function in transcriptional regulation. Our results have provided novel insights into the molecular mechanisms of PCD in plants, especially under ER stress conditions.
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