Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 10; pp. 3994 - 3999
• Main Authors: Tatchell, Kelly, Makrantoni, Vasso, Stark, Michael J.R, Robinson, Lucy C
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.03.2011; National Acad Sciences
• Subjects: Anaphase; aurora B protein; Aurora Kinases; Biological Sciences; Catalytic subunits; Cell growth; Cell Nucleus - metabolism; Chromosome Deletion; Chromosome segregation; Chromosomes; Chromosomes, Fungal; Fidelity; Fluorescence; Gene expression regulation; Genes; Genetic mutation; Genetics; Histone H3; Intracellular Signaling Peptides and Proteins - genetics; Kinetochores; Mutation; Nuclear division; Nutritional status; Phosphatases; Phosphatidylinositol 3-Kinases - genetics; Phosphorylation; protein phosphatase; Protein Phosphatase 1 - metabolism; Protein-Serine-Threonine Kinases - genetics; Proteins; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Spindles; Temperature; Temperature effects; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1014406108

Ipl1/Aurora B is the catalytic subunit of a complex that is required for chromosome segregation and nuclear division. Before anaphase, Ipl1 localizes to kinetochores, where it is required to establish proper kinetochore-microtubule associations and regulate the spindle assembly checkpoint. The protein phosphatase Glc7/PP1 opposes Ipl1 for some of these activities. To more thoroughly characterize the Glc7 phosphatase that opposes Ipl1, we have identified mutations that suppress the thermosensitivity of an ipl1-2 mutant. In addition to mutations in genes previously associated with ipl1 suppression, we recovered a null mutant in TCO89, which encodes a subunit of the TOR complex 1 (TORC1), the conserved rapamycin-sensitive kinase activity that regulates cell growth in response to nutritional status. The temperature sensitivity of ipl1-2 can also be suppressed by null mutation of TOR1 or by administration of pharmacological TORC1 inhibitors, indicating that reduced TORC1 activity is responsible for the suppression. Suppression of the ipl1-2 growth defect is accompanied by increased fidelity of chromosome segregation and increased phosphorylation of the Ipl1 substrates histone H3 and Dam1. Nuclear Glc7 levels are reduced in a tco89 mutant, suggesting that TORC1 activity is required for the nuclear accumulation of Glc7. In addition, several mutant GLC7 alleles that suppress the temperature sensitivity of ipl1-2 exhibit negative synthetic genetic interactions with TORC1 mutants. Together, our results suggest that TORC1 positively regulates the Glc7 activity that opposes Ipl1 and provide a mechanism to tie nutritional status with mitotic regulation.