Study of Protein Stability Synthesized in the Endoplasmic Reticulum

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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.