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 I 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 I (GLO1) in Saccharomyces cerevisiae. Here we show that the expression of GLO1 is induced following treatment with CaCl2 dependent on Hog1-MAP kinase 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 defective in calcineurin or defective in the sole transcription factor functioning under the control of calcineurin (crz1) 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 Ca2+ signaling 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, that in cells overexpressing CRZ1 was greatly reduced, but increased markedly when FK506 was present. We found that the levels of Msn2 and Msn4 proteins in CaCl2-treated cells decreased gradually, and FK506 blocked the degradation of Msn2/Msn4. Here we propose that Crz1 destabilizes Msn2/Msn4 in the nucleus of cells in response to Ca2+ signaling.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|