The unfolded protein response: the dawn of a new field.
The unfolded protein response: the dawn of a new field.
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DOI：
10.2183/pjab.91.469
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发表时间：
2015
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影响因子：
--
通讯作者：
Mori K
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文献类型：
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作者：
Mori K
未折叠蛋白反应（UPR）这一全新的研究领域于1988年诞生，起源于哺乳动物培养细胞的癌症研究。UPR是一种转录诱导程序，与从内质网（ER）到细胞核的细胞内信号相结合，以维持内质网的稳态，内质网是一种控制用于分泌途径的蛋白质质量的细胞器。利用出芽酵母（Saccharomyces cerevisiae）进行的极竞争性分析显示，尽管内质网和细胞表面的信号都是通过跨膜蛋白激酶的激活启动的，但内质网驻留的Ire1p （UPR的传感器分子）下游的机制是独特的。因此，利用非常规剪接体独立的mRNA剪接来产生高活性转录因子Hac1p。这是一个自传式的故事，讲述了在普遍定期审议研究的早期，一位年轻的、尚未独立的科学家如何与一位非常著名的正教授竞争，最终导致他们在2014年分享拉斯克基础医学研究奖。
Originating from cancer research in mammalian cultured cells, the entirely new field of the unfolded protein response (UPR) was born in 1988. The UPR is a transcriptional induction program coupled with intracellular signaling from the endoplasmic reticulum (ER) to the nucleus to maintain the homeostasis of the ER, an organelle which controls the quality of proteins destined for the secretory pathway. Extremely competitive analyses using the budding yeast Saccharomyces cerevisiae revealed that although signaling from both the ER and cell surface is initiated by activation of a transmembrane protein kinase, the mechanism downstream of ER-resident Ire1p, a sensor molecule of the UPR, is unique. Thus, unconventional spliceosome-independent mRNA splicing is utilized to produce the highly active transcription factor Hac1p. This is the autobiographical story of how a young and not yet independent scientist competed with a very famous full professor in the early days of UPR research, which ultimately lead to their sharing Lasker Basic Medical Research Award in 2014.