Multiple pathways regulating fission yeast mitosis upon environmental stresses.
Environmental signals, such as nutrient availability and physiological stresses, modulate the cell cycle and cell size of the fission yeast Schizosaccharomyces pombe. However, little is known about how these signals are transmitted to the central cell cycle regulator, Cdc2, the cyclin-dependent kinase that induces mitosis. We show here genetic evidence that medium alkalization stimulates mitosis and consequently reduces cell size, either through the Nim1-Wee1 cascade, which regulates the inhibitory phosphorylation of Cdc2 at Tyr(15), or through the Cdc2-activating phosphatase, Cdc25. Alkaline stress stimulates phosphorylation of Nim1, accumulation of Cdc25 and dephosphorylation of Cdc2 at Tyr(15). We also show that osmostress stimulates mitosis through two independent pathways: one stimulates accumulation of Cdc25, and another dephosphorylation of Cdc2 at Tyr(15). However, our analysis demonstrates that these environmental stresses can stimulate mitosis independently of dephosphorylation of Cdc2 at Tyr(15). The S. pombe MAP kinase, Spc1, was required for the steady-state level of Cdc25 in the normal cell cycle and for its accumulation in response to alkaline stress and nutritional starvation.
Kishimoto
N
N
Center for Gene Science, Hiroshima University, Kagamiyama 1-4-2, Higashi-hiroshima 739-8527, Japan.
Yamashita
I
I
D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins; D009997:Osmotic Pressure; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1 / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1; C080364:cdr1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase