TOR signalling regulates mitotic commitment through the stress MAP kinase pathway and the Polo and Cdc2 kinases.
The coupling of growth to cell cycle progression allows eukaryotic cells to divide at particular sizes depending on nutrient availability. In fission yeast, this coupling involves the Spc1/Sty1 mitogen-activated protein kinase (MAPK) pathway working through Polo kinase recruitment to the spindle pole bodies (SPBs). Here we report that changes in nutrients influence TOR signalling, which modulates Spc1/Sty1 activity. Rapamycin-induced inhibition of TOR signalling advanced mitotic onset, mimicking the reduction in cell size at division seen after shifts to poor nitrogen sources. Gcn2, an effector of TOR signalling and modulator of translation, regulates the Pyp2 phosphatase that in turn modulates Spc1/Sty1 activity. Rapamycin- or nutrient-induced stimulation of Spc1/Sty1 activity promotes Polo kinase SPB recruitment and Cdc2 activation to advance mitotic onset. This advanced mitotic onset is abolished in cells depleted of Gcn2, Pyp2, or Spc1/Sty1 or on blockage of Spc1/Sty1-dependent Polo SPB recruitment. Therefore, TOR signalling modulates mitotic onset through the stress MAPK pathway via the Pyp2 phosphatase.
Petersen
Janni
J
The Rockefeller University, Box 5, 1230 York Avenue, New York, NY 10021, USA. Janni.Petersen@manchester.ac.uk
Nurse
Paul
P
D016203:CDC2 Protein Kinase / Q000502:physiology*; D002478:Cells, Cultured; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D008938:Mitosis / Q000187:drug effects; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012568:Schizosaccharomyces / Q000166:cytology; D029702:Schizosaccharomyces pombe Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D020123:Sirolimus / Q000494:pharmacology
D029702:Schizosaccharomyces pombe Proteins; D011494:Protein Kinases; C523461:Tor1 protein, S pombe; C501407:Plo1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C469447:cdc2 protein, S pombe; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe; D020123:Sirolimus