The Stress-activated Mitogen-activated Protein Kinase Signaling Cascade Promotes Exit from Mitosis

Abstract

In budding yeast, a signaling network known as the mitotic exit network (MEN) triggers exit from mitosis. We find that hypertonic stress allows MEN mutants to exit from mitosis in a manner dependent on the high osmolarity glycerol (HOG) mitogen-activated protein (MAP) kinase cascade. The HOG pathway drives exit from mitosis in MEN mutants by promoting the activation of the MEN effector, the protein phosphatase Cdc14. Activation of Cdc14 depends on the Cdc14 early anaphase release network, a group of proteins that functions in parallel to the MEN to promote Cdc14 function. Notably, exit from mitosis is promoted by the signaling branch defined by the Sho1 osmosensing system, but not by the Sln1 osmosensor of the HOG pathway. Our results suggest that the stress MAP kinase pathway mobilizes programs to promote completion of the cell cycle and entry into G 1 under unfavorable conditions.

Regulation of Mitotic Spindle Disassembly by an Environmental Stress-Sensing Pathway in Budding Yeast

“…Interestingly, a deletion mutant of SHO1, which encodes an osmosensor, showed negative genetic interactions with both kip3D and cdh1D mutants. Sho1 is a transmembrane protein component of the HOG pathway that acts as a sensor of osmotic (sorbitol) stress (Brewster et al 1993;Maeda et al 1995;Posas and Saito 1997;Raitt et al 2000;Reiser et al 2006;Cullen et al 2004; reviewed in Schwartz and Madhani 2004;Clotet and Posas 2007). Cells exposed to 1 M sorbitol initiate a Sho1-dependent MAPK (mitogen-activated protein kinase) signaling cascade that requires the scaffold Ste11, Msb2, and the MAPKK Pbs2.…”

“…Moreover, Hog1 activation also inhibits cyclin-Cdk1 activity, which delays G2 (Alexander et al 2001). HOG pathway activation has also been shown to promote mitotic exit (Reiser et al 2006). Shocking cells osmotically with medium containing sorbitol rescues the anaphase arrest of cdc15-2 mutants in a SHO1-dependent manner.…”

“…We used the sensitized background of a cdc15-2 mutant, a temperaturesensitive allele of the mitotic exit network kinase Cdc15. Growing cdc15-2 cells on medium containing sorbitol rescues the temperature sensitivity of the allele in a HOG pathway-dependent manner (Reiser et al 2006; Figure S4A). We found that, like HOG1 and PBS2, SHE1 contributed to the rescue of the cdc15-2 mutant on sorbitol plates ( Figure S4A) although less robustly than HOG pathway genes.…”

“…However, when we synchronized cells with hydroxyurea, and collected cells in a time-course fashion after washout, we were able to detect some changes in She1 phosphorylation in hog1D cells ( Figure S4F). One phosphorylated species in particular seems to be reduced in hog1D cells ( Figure S4F, see arrow).Cdc14 localization is perturbed in she1D and hog1D cells PBS2 is required for mitotic exit in a cdc15-2 mutant exposed to sorbitol stress, and this escape from a cdc15-2 arrest is dependent on Cdc14 release from the mother cell nucleolus (Reiser et al 2006). In agreement with Reiser et al (2006), we found that the pbs2D mutant, as well as hog1D and she1-D mutants, did not show marked delays in Cdc14 release from the mother cell nucleolus in nonstress conditions.…”

“…Shocking cells osmotically with medium containing sorbitol rescues the anaphase arrest of cdc15-2 mutants in a SHO1-dependent manner. This rescue has been linked to the Pbs2-dependent HOG Pathway Promotes Spindle Disassembly 1045 release of Cdc14 phosphatase from the nucleolus (Reiser et al 2006). We further examined the genetic and physical interaction profiles of HOG pathway components ( Figure 1B).…”