Study of Protein Stability Synthesized in the Endoplasmic Reticulum

本研究旨在阐明内质网合成蛋白稳定性的决定机制。特别是以拟南芥为研究对象，对植物内质网胁迫反应的分子机制进行了深入的研究。虽然最初的突变体筛选方法没有成功，但可以利用拟南芥的基因组信息分离出bZIP型转录因子AtbZIP60。AtbZIP60是第一个调控植物内质网胁迫反应的转录因子。AtbZIP60的调控是非常独特的。也就是说，在非应激条件下，AtbZIP60蛋白被认为定位于内质网膜。当植物细胞感知内质网胁迫时，AtbZIP60蛋白以未知的机制发生断裂。AtbZIP60的n端易位到细胞核中，作为转录因子激活内质网应激反应诱导的基因。该调控机制是植物科学领域的首次发现，是本研究的一大贡献。下一步将进一步明确AtbZIP60蛋白的裂解机制。由于S1P和S2P蛋白酶似乎不参与这一过程，替代蛋白酶被认为起作用。根据对一个T-DNA插入突变体的分析结果，可以清楚地看出AtbZIP60调控内质网络胁迫诱导的基因表达，如AtBiP3。然而，AtbZIP60并不是调节内质网应激反应的唯一转录因子。鉴定另一种转录因子将是一项具有挑战性和重要的未来研究。

This study aimed to clarify the mechanism to determine the stability of protein which is synthesized in the endoplasmic reticulum. Specifically major research was conducted to understand the molecular mechanism of the-ER stress response of plants using Arabidopsis. Although initial approach that is mutant screening did not work, a bZIP type transcription factor AtbZIP60 could be isolated using genomic information of Arabidopsis. AtbZIP60 is the first transcription factor that regulated the ER stress response in plants. Regulation of AtbZIP60 is very unique. That is, AtbZIP60 protein is considered to localize to the ER membrane under non-stressed condition. When plant cells perceive the ER stress, AtbZIP60 protein is cleaved by unknown mechanism. The N-terminal region of AtbZIP60 translocates to the nucleus to in order to function as a transcription factor that activates genes that are induced upon the ER stress response. Such regulation mechanism is the first finding in plant science field and is considered to be a great contribution of this study. Next step would be clarification of cleavage mechanism of AtbZIP60 protein. Since, S1P and S2P proteases do not seem to be involved in this process, alternative proteases are considered to function. According to the results of analysis of a T-DNA insertion mutant, it is clear that AtbZIP60 regulates the expression of genes induced by the ER stress, such as AtBiP3. However, it also became clear that AtbZIP60 is not an only transcription factor regulating the ER stress response. Identification of another transcription factor would be a challenging and important future study.