Study of Protein Stability Synthesized in the Endoplasmic Reticulum

本研究旨在阐明决定内质网合成蛋白质稳定性的机制。具体地说，主要研究了拟南芥对植物内质网胁迫反应的分子机制。虽然最初的方法即突变体筛选并不奏效，但利用拟南芥的基因组信息可以分离到一个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，AtbZIP60蛋白被认为在非应激条件下定位于内质网细胞膜。当植物细胞感受到内质网胁迫时，AtbZIP60蛋白被未知的机制切割。AtbZIP60的N-末端区域移位到核TO，以发挥转录因子的功能，激活在内质网应激反应中诱导的基因。这种调控机制是植物科学领域的首次发现，被认为是本研究的一大贡献。下一步将阐明AtbZIP60蛋白的切割机制。由于S1P和S2P蛋白水解酶似乎不参与这一过程，因此认为替代蛋白水解酶起作用。根据对一个T-DNA插入突变体的分析结果表明，AtbZIP60调控ER胁迫诱导的基因的表达，如AtBiP3。然而，也很清楚，AtbZIP60并不是唯一调节内质网应激反应的转录因子。另一种转录因子的鉴定将是一个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.