复旦大学在PLOS子刊首次揭示转录因子NAC089调控内质网胁迫应答机

内质网是所有分泌蛋白和大部分膜蛋白合成和折叠的场所。蛋白质的折叠是一个精细调控的过程，当内质网内错误折叠蛋白大量积累时可引起内质网胁迫应答(也叫未折叠蛋白应答，UPR)，通过调控一系列下游基因的表达来帮助蛋白质的折叠或促进错误折叠蛋白的降解。该应答不但与很多人类疾病密切相关，而且在植物发育、抗逆、抗病等过程中发挥了重要的作用。

当内质网胁迫严重的时候，内质网胁迫应答也会引起PCD，但目前对其分子机制的理解非常有限。刘建祥课题组利用细胞生物学和生物化学等方法在模式植物拟南芥中发现内质网胁迫诱导一个膜结合转录因子NAC089从内质网膜上转移到细胞核中。遗传分析等实验证明NAC089调控了内质网胁迫诱导的PCD。

基因表达分析和染色质免疫共沉淀等实验更进一步证明NAC089能够调控PCD相关的基因表达。NAC089基因本身的表达也受内质网胁迫的上调，此过程受另外两个促进细胞生存的膜结合转录因子bZIP28和bZIP60的直接调控。该论文第一作者为博士研究生杨正婷，通讯作者为刘建祥老师。该研究得到了科技部、国家自然科学基金和教育部博士点基金等项目资助。

刘建祥课题组长期从事植物逆境生物学的研究，近年来在植物内质网胁迫应答领域取得了一系列研究成果，已在PLOS Genetics、Plant Cell、Plant Journal、Molecular Plant等国际学术期刊发表多篇通讯作者论文。

原文摘要：

The Membrane-Associated Transcription Factor NAC089 Controls ER-Stress-Induced Programmed Cell Death in Plants

Zheng-Ting Yang, Mei-Jing Wang, Ling Sun, Sun-Jie Lu, Dong-Ling Bi, Le Sun, Ze-Ting Song, Shuang-Shuang Zhang, Shun-Fan Zhou, Jian-Xiang Liu

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.

标签: 程序性细胞死亡 内质网胁迫应答 膜结合转录因子 NAC089

作者：复旦大学

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