Calcineurin/Crz1 destabilizes Msn2 and Msn4 in the nucleus in response to Ca(2+) in Saccharomyces cerevisiae.
Although methylglyoxal is derived from glycolysis, it has adverse effects on cellular function. Hence, the intrinsic role of methylglyoxal in vivo remains to be determined. Glyoxalase 1 is a pivotal enzyme in the metabolism of methylglyoxal in all types of organisms. To learn about the physiological roles of methylglyoxal, we have screened conditions that alter the expression of the gene encoding glyoxalase 1, GLO1, in Saccharomyces cerevisiae. We show that the expression of GLO1 is induced following treatment with Ca2+ and is dependent on the MAPK (mitogen-activated protein kinase) Hog1 protein and the Msn2/Msn4 transcription factors. Intriguingly, the Ca2+-induced expression of GLO1 was enhanced in the presence of FK506, a potent inhibitor of calcineurin. Consequently, the Ca2+-induced expression of GLO1 in a mutant that is defective in calcineurin or Crz1, the sole transcription factor downstream of calcineurin, was much greater than that in the wild-type strain even without FK506. This phenomenon was dependent upon a cis-element, the STRE (stress-response element), in the promoter that is able to mediate the response to Ca2+ signalling together with Hog1 and Msn2/Msn4. The level of Ca2+-induced expression of GLO1 reached a maximum in cells overexpressing MSN2 even when FK506 was not present, whereas in cells overexpressing CRZ1 the level was greatly reduced and increased markedly when FK506 was present. We also found that the levels of Msn2 and Msn4 proteins in Ca2+-treated cells decreased gradually and that FK506 blocked the degradation of Msn2/Msn4. We propose that Crz1 destabilizes Msn2/Msn4 in the nuclei of cells in response to Ca2+ signalling.
Takatsume
Yoshifumi
Y
Kyoto University, Uji, Japan.
Ohdate
Takumi
T
Maeta
Kazuhiro
K
Nomura
Wataru
W
Izawa
Shingo
S
Inoue
Yoshiharu
Y
D019703:Calcineurin / Q000502:physiology*; D020013:Calcium Signaling; D002467:Cell Nucleus; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D007791:Lactoylglutathione Lyase / Q000235:genetics; D055550:Protein Stability; D011765:Pyruvaldehyde; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
C109868:CRZ1 protein, S cerevisiae; D004268:DNA-Binding Proteins; C081935:MSN2 protein, S cerevisiae; C081937:MSN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D011765:Pyruvaldehyde; D019703:Calcineurin; D007791:Lactoylglutathione Lyase