Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, 08003 Barcelona, Spain.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):8924-8933. doi: 10.1073/pnas.1918308117. Epub 2020 Apr 7.
Adaptation to environmental changes is crucial for cell fitness. In , variations in external osmolarity trigger the activation of the stress-activated protein kinase Hog1 (high-osmolarity glycerol 1), which regulates gene expression, metabolism, and cell-cycle progression. The activation of this kinase leads to the regulation of G1, S, and G2 phases of the cell cycle to prevent genome instability and promote cell survival. Here we show that Hog1 delays mitotic exit when cells are stressed during metaphase. Hog1 phosphorylates the nucleolar protein Net1, altering its affinity for the phosphatase Cdc14, whose activity is essential for mitotic exit and completion of the cell cycle. The untimely release of Cdc14 from the nucleolus upon activation of Hog1 is linked to a defect in ribosomal DNA (rDNA) and telomere segregation, and it ultimately delays cell division. A mutant of Net1 that cannot be phosphorylated by Hog1 displays reduced viability upon osmostress. Thus, Hog1 contributes to maximizing cell survival upon stress by regulating mitotic exit.
适应环境变化对于细胞的适应性至关重要。在这种情况下，外部渗透压的变化会触发应激激活蛋白激酶 Hog1（高渗透压甘油 1）的激活，该激酶调节基因表达、代谢和细胞周期进程。该激酶的激活导致细胞周期的 G1、S 和 G2 期的调节，以防止基因组不稳定性并促进细胞存活。在这里，我们表明 Hog1 在细胞在有丝分裂中期受到压力时会延迟有丝分裂退出。Hog1 磷酸化核仁蛋白 Net1，改变其与磷酸酶 Cdc14 的亲和力，Cdc14 的活性对于有丝分裂退出和细胞周期完成至关重要。Hog1 激活时 Cdc14 从核仁的过早释放与核糖体 DNA（rDNA）和端粒分离缺陷有关，并最终延迟细胞分裂。不能被 Hog1 磷酸化的 Net1 突变体在渗透压应激下表现出降低的生存能力。因此，Hog1 通过调节有丝分裂退出来促进应激时细胞的最大存活。
