Mitogen-activated protein kinase Hog1 mediates adaptation to G1 checkpoint arrest during arsenite and hyperosmotic stress.
Cells slow down cell cycle progression in order to adapt to unfavorable stress conditions. Yeast (Saccharomyces cerevisiae) responds to osmotic stress by triggering G(1) and G(2) checkpoint delays that are dependent on the mitogen-activated protein kinase (MAPK) Hog1. The high-osmolarity glycerol (HOG) pathway is also activated by arsenite, and the hog1Delta mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1Delta cells. Yeast cell cycle regulation in response to arsenite and the role of Hog1 in this process have not yet been analyzed. Here, we found that long-term exposure to arsenite led to transient G(1) and G(2) delays in wild-type cells, whereas cells that lack the HOG1 gene or are defective in Hog1 kinase activity displayed persistent G(1) cell cycle arrest. Elevated levels of intracellular arsenite and "cross talk" between the HOG and pheromone response pathways, observed in arsenite-treated hog1Delta cells, prolonged the G(1) delay but did not cause a persistent G(1) arrest. In contrast, deletion of the SIC1 gene encoding a cyclin-dependent kinase inhibitor fully suppressed the observed block of G(1) exit in hog1Delta cells. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1Delta cells. Interestingly, Sic1-dependent persistent G(1) arrest was also observed in hog1Delta cells during hyperosmotic stress. Taken together, our data point to an important role of the Hog1 kinase in adaptation to stress-induced G(1) cell cycle arrest.
Migdal
Iwona
I
Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland.
Ilina
Yulia
Y
Tamás
Markus J
MJ
Wysocki
Robert
R
D000222:Adaptation, Physiological / Q000235:genetics*; D018053:Arsenites / Q000494:pharmacology; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D018816:Genes, cdc / Q000187:drug effects / Q000502:physiology*; D006982:Hypertonic Solutions / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009997:Osmotic Pressure / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013723:Teratogens / Q000494:pharmacology
D018053:Arsenites; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D006982:Hypertonic Solutions; C086926:SIC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013723:Teratogens; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; C015001:arsenite