Interdisciplinary Program for Bioengineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Interdisciplinary Program for Bioengineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea; School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Biochim Biophys Acta Gene Regul Mech. 2017 Jun;1860(6):695-704. doi: 10.1016/j.bbagrm.2017.03.003. Epub 2017 Mar 19.
CK2 is a highly conserved Ser/Thr protein kinase involved in a large number of cellular processes. Here, we demonstrate that CK2-dependent phosphorylation positively regulates Msn2/4, the general stress response transcriptional activators in Saccharomyces cerevisiae, in response to various types of environmental stress conditions. CK2 overexpression elicits hyperactivation of Msn2/4, whereas deletion of one of the CK2 catalytic subunits, especially CKA2, leads to reduced transcriptional activity of Msn2/4 in response to glucose starvation, HO and lactic acid. The CKA2 deletion mutant also shows increased stress sensitivity. CK2 phosphorylates Ser194 and Ser638 in Msn2 and replacement of Ser638 with alanine leads to reduced Msn2 activity upon stress and reduced tolerance to HO and lactic acid. CKA2 deletion mutant shows shorter nuclear retention time of Msn2 upon lactic acid stress, suggesting that CK2 might regulate nuclear localization of Msn2. However, Msn2 mutant shows normal nuclear import and export patterns upon stress, suggesting that CK2 might positively regulate the general stress response not only by direct phosphorylation of Msn2/4, but also by regulating cellular translocation machinery.
CK2 是一种高度保守的丝氨酸/苏氨酸蛋白激酶，参与了许多细胞过程。在这里，我们证明 CK2 依赖性磷酸化正向调节酵母中的一般应激反应转录激活因子 Msn2/4，以响应各种环境应激条件。CK2 的过表达引起 Msn2/4 的过度激活，而 CK2 的一个催化亚基（尤其是 CKA2）的缺失导致葡萄糖饥饿、HO 和乳酸响应时 Msn2/4 的转录活性降低。CKA2 缺失突变体也表现出更高的应激敏感性。CK2 磷酸化 Msn2 的 Ser194 和 Ser638，而将 Ser638 替换为丙氨酸会导致应激时 Msn2 活性降低，对 HO 和乳酸的耐受性降低。CKA2 缺失突变体在乳酸应激下显示出 Msn2 的核保留时间缩短，表明 CK2 可能通过调节 Msn2 的核定位来调节一般应激反应。然而，Msn2 突变体在应激下表现出正常的核输入和输出模式，这表明 CK2 不仅可以通过 Msn2/4 的直接磷酸化，还可以通过调节细胞易位机制来正向调节一般应激反应。
