González-Novo Alberto, Jiménez Javier, Clotet Josep, Nadal-Ribelles Mariona, Cavero Santiago, de Nadal Eulàlia, Posas Francesc
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain Departament de Ciències Bàsiques, Facultat de Medicina i Ciències de la Salut, Universitat Internacional de Catalunya, Barcelona, Spain.
Mol Cell Biol. 2015 May;35(9):1606-18. doi: 10.1128/MCB.01279-14. Epub 2015 Mar 2.
Yeast cells have developed complex mechanisms to cope with extracellular insults. An increase in external osmolarity leads to activation of the stress-activated protein kinase Hog1, which is the main regulator of adaptive responses, such as gene expression and cell cycle progression, that are essential for cellular survival. Upon osmostress, the G1-to-S transition is regulated by Hog1 through stabilization of the cyclin-dependent kinase inhibitor Sic1 and the downregulation of G1 cyclin expression by an unclear mechanism. Here, we show that Hog1 interacts with and phosphorylates components of the core cell cycle transcriptional machinery such as Whi5 and the coregulator Msa1. Phosphorylation of these two transcriptional regulators by Hog1 is essential for inhibition of G1 cyclin expression, for control of cell morphogenesis, and for maximal cell survival upon stress. The control of both Whi5 and Msa1 by Hog1 also revealed the necessity for proper coordination of budding and DNA replication. Thus, Hog1 regulates G1 cyclin transcription upon osmostress to ensure coherent passage through Start.
酵母细胞已形成复杂的机制来应对细胞外的损伤。外部渗透压的增加会导致应激激活蛋白激酶Hog1的激活，Hog1是适应性反应（如基因表达和细胞周期进程）的主要调节因子，这些反应对细胞存活至关重要。在渗透应激下，Hog1通过稳定细胞周期蛋白依赖性激酶抑制剂Sic1以及通过不明机制下调G1期细胞周期蛋白的表达来调节G1期到S期的转变。在这里，我们表明Hog1与核心细胞周期转录机制的成分（如Whi5和共调节因子Msa1）相互作用并使其磷酸化。Hog1对这两种转录调节因子的磷酸化对于抑制G1期细胞周期蛋白的表达、控制细胞形态发生以及在应激时实现最大细胞存活至关重要。Hog1对Whi5和Msa1的控制也揭示了正确协调出芽和DNA复制的必要性。因此，Hog1在渗透应激时调节G1期细胞周期蛋白的转录，以确保连贯通过起始点。
