Stowers Institute for Medical Research, Kansas City, United States.
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, United States.
Elife. 2020 Dec 29;9:e64588. doi: 10.7554/eLife.64588.
Changes in available nutrients are inevitable events for most living organisms. Upon nutritional stress, several signaling pathways cooperate to change the transcription program through chromatin regulation to rewire cellular metabolism. In budding yeast, histone H3 threonine 11 phosphorylation (H3pT11) acts as a marker of low glucose stress and regulates the transcription of nutritional stress-responsive genes. Understanding how this histone modification 'senses' external glucose changes remains elusive. Here, we show that Tda1, the yeast ortholog of human Nuak1, is a direct kinase for H3pT11 upon low glucose stress. Yeast AMP-activated protein kinase (AMPK) directly phosphorylates Tda1 to govern Tda1 activity, while CK2 regulates Tda1 nuclear localization. Collectively, AMPK and CK2 signaling converge on histone kinase Tda1 to link external low glucose stress to chromatin regulation.
对于大多数生物体来说，可利用营养物质的变化是不可避免的事件。在营养压力下，几种信号通路通过染色质调节合作改变转录程序，以重新布线细胞代谢。在 budding yeast 中，组蛋白 H3 苏氨酸 11 磷酸化（H3pT11）作为低糖应激的标志物，并调节营养应激反应基因的转录。然而，这种组蛋白修饰如何“感知”外部葡萄糖变化仍然难以捉摸。在这里，我们表明，酵母 Nuak1 的同源物 Tda1 在低糖应激下是 H3pT11 的直接激酶。酵母 AMP 激活蛋白激酶（AMPK）直接磷酸化 Tda1 以控制 Tda1 活性，而 CK2 调节 Tda1 的核定位。总之，AMPK 和 CK2 信号通路汇聚到组蛋白激酶 Tda1 上，将外部低糖应激与染色质调节联系起来。
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