Leber Jess H, Bernales Sebastián, Walter Peter
Department of Biochemistry and Biophysics, University of California, San Francisco, USA.
PLoS Biol. 2004 Aug;2(8):E235. doi: 10.1371/journal.pbio.0020235. Epub 2004 Aug 17.
Nonconventional splicing of the gene encoding the Hac1p transcription activator regulates the unfolded protein response (UPR) in Saccharomyces cerevisiae. This simple on/off switch contrasts with a more complex circuitry in higher eukaryotes. Here we show that a heretofore unrecognized pathway operates in yeast to regulate the transcription of HAC1. The resulting increase in Hac1p production, combined with the production or activation of a putative UPR modulatory factor, is necessary to qualitatively modify the cellular response in order to survive the inducing conditions. This parallel endoplasmic reticulum-to-nucleus signaling pathway thereby serves to modify the UPR-driven transcriptional program. The results suggest a surprising conservation among all eukaryotes of the ways by which the elements of the UPR signaling circuit are connected. We show that by adding an additional signaling element to the basic UPR circuit, a simple switch is transformed into a complex response.
编码Hac1p转录激活因子的基因的非常规剪接调节酿酒酵母中的未折叠蛋白反应（UPR）。这种简单的开/关开关与高等真核生物中更复杂的信号通路形成对比。在这里，我们表明，酵母中存在一条迄今为止未被认识的调节HAC1转录的途径。Hac1p产量的增加，与一种假定的UPR调节因子的产生或激活相结合，对于定性改变细胞反应以在诱导条件下存活是必要的。这种平行的内质网到细胞核的信号通路从而有助于改变由UPR驱动的转录程序。结果表明，在所有真核生物中，UPR信号回路元件的连接方式存在惊人的保守性。我们表明，通过在基本的UPR回路中添加一个额外的信号元件，一个简单的开关就转变为一个复杂的反应。
