CK2-dependent phosphorylation positively regulates stress-induced activation of Msn2 in Saccharomyces cerevisiae.
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, H2O2,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 H2O2and 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, Msn2S194A, S638Amutant 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.
Interdisciplinary Program for Bioengineering, Institute of Chemical Processes, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Bo-Ram
BR
Cho
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. Electronic address: hahnjs@snu.ac.kr.
Ji-Sook
JS
Hahn
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D019943:Amino Acid Substitution; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020125:Mutation, Missense; D010766:Phosphorylation / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C000593617:CKa2 protein, S cerevisiae; D047390:Casein Kinase II
CK2; Msn2; Msn4; Saccharomyces cerevisiae; Stress response