Polo kinase links the stress pathway to cell cycle control and tip growth in fission yeast.
Stress-activated mitogen-activated protein kinase cascades instigate a range of changes to enable eukaryotic cells to cope with particular insults. In Schizosaccharomyces pombe these responses include the transcription of specific gene sets and inhibition of entry into mitosis. The S. pombe stress response pathway (SRP) also promotes commitment to mitosis in unperturbed cell cycles to allow cells to match their rate of division with nutrient availability. The nature of this SRP function in cell cycle control is unknown. Entry into mitosis is controlled by mitosis-promoting factor (MPF; Cdc2/cyclin B) activity. Inhibitory phosphorylation of Cdc2 by Wee1 kinase inactivates MPF until Cdc25 removes this phosphate to promote mitosis. The balance between Wee1 and Cdc25 activities is influenced by the recruitment of polo kinase (Plo1) to the spindle pole body (SPB). The SPB component Cut12 mediates this recruitment. Hyper-activating mutations in either cut12 or plo1 enable Cdc25-defective cells to enter mitosis. The hyperactive cut12.s11 mutation suppresses cdc25.22, as it promotes recruitment of active Plo1 to interphase SPBs. Here we show that the SRP promotes phosphorylation of Plo1 on Ser 402. In unperturbed cell cycles, SRP-mediated phosphorylation of Ser 402 promotes Plo1 recruitment to SPBs and thus commitment to mitosis. Ser 402 phosphorylation also ensures efficient reinitiation of cell tip growth and cell division during recovery from particular stresses. Thus, phosphorylation of Plo1 Ser 402 not only enables SRP signalling to modulate the timing of mitotic commitment in response to nutrient status in unperturbed cycles, but also promotes the return to normal cell cycle control after stress.
Petersen
Janni
J
Cancer Research UK Cell Division Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 4BX, UK.
Hagan
Iain M
IM
D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D013696:Temperature
D029702:Schizosaccharomyces pombe Proteins; D010768:Phosphoserine; C501407:Plo1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe