The budding yeast protein kinase Ipl1/Aurora allows the absence of tension to activate the spindle checkpoint.
The spindle checkpoint prevents cell cycle progression in cells that have mitotic spindle defects. Although several spindle defects activate the spindle checkpoint, the exact nature of the primary signal is unknown. We have found that the budding yeast member of the Aurora protein kinase family, Ipl1p, is required to maintain a subset of spindle checkpoint arrests. Ipl1p is required to maintain the spindle checkpoint that is induced by overexpression of the protein kinase Mps1. Inactivating Ipl1p allows cells overexpressing Mps1p to escape from mitosis and segregate their chromosomes normally. Therefore, the requirement for Ipl1p in the spindle checkpoint is not a consequence of kinetochore and/or spindle defects. The requirement for Ipl1p distinguishes two different activators of the spindle checkpoint: Ipl1p function is required for the delay triggered by chromosomes whose kinetochores are not under tension, but is not required for arrest induced by spindle depolymerization. Ipl1p localizes at or near kinetochores during mitosis, and we propose that Ipl1p is required to monitor tension at the kinetochore.
Biggins
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Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. sbiggins@fhcrc.org
Murray
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D064127:Aurora Kinases; D001696:Biomechanical Phenomena; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D020090:Chromosome Segregation / Q000187:drug effects; D015825:Chromosomes, Fungal / Q000187:drug effects; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins; D018386:Kinetochores / Q000187:drug effects / Q000378:metabolism; D008677:Metaphase / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors
D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D064127:Aurora Kinases; C576961:IPL1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C093416:MPS1 protein, S cerevisiae; D015739:Nocodazole