Departament de Ciències Experimentals i de la Salut, Cell Signalling Unit, Universitat Pompeu Fabra (UPF), Barcelona, Spain.
EMBO J. 2011 Jul 8;30(16):3274-84. doi: 10.1038/emboj.2011.227.
Protein ubiquitylation is a key process in the regulation of many cellular processes. The balance between the activity of ubiquitin ligases and that of proteases controls the level of ubiquitylation. In response to extracellular stimuli, stress-activated protein kinases (SAPK) modulate gene expression to maximize cell survival. In yeast, the Hog1 SAPK has a key role in reprogramming the gene expression pattern required for cell survival upon osmostress. Here, we show that the Ubp3 ubiquitin protease is a target for the Hog1 SAPK to modulate gene expression. ubp3 mutant cells are defective in expression of osmoresponsive genes. Hog1 interacts with and phosphorylates Ubp3 at serine 695, which is essential to determine the extent of transcriptional activation in response to osmostress. Furthermore, Ubp3 is recruited to osmoresponsive genes to modulate transcriptional initiation as well as elongation. Therefore, Ubp3 activity responds to external stimuli and is required for transcriptional activation upon osmostress.
蛋白质泛素化是调节许多细胞过程的关键过程。泛素连接酶和蛋白酶活性之间的平衡控制着泛素化的水平。在细胞外刺激的响应下，应激激活蛋白激酶（SAPK）调节基因表达以最大化细胞存活。在酵母中，Hog1 SAPK 在细胞存活所需的基因表达模式的重编程中起关键作用。在这里，我们表明 Ubp3 泛素蛋白酶是 Hog1 SAPK 调节基因表达的靶标。ubp3 突变细胞在渗透压响应基因的表达上存在缺陷。Hog1 与 Ubp3 相互作用并在丝氨酸 695 处磷酸化 Ubp3，这对于确定对渗透压胁迫的转录激活程度至关重要。此外，Ubp3 被招募到渗透压响应基因，以调节转录起始以及延伸。因此，Ubp3 的活性响应外部刺激，并且在渗透压胁迫时需要进行转录激活。
