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.
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http://dx.doi.org/10.1073/pnas.1014406108 | DOI Listing |
Nat Commun
December 2021
School of Biological and Chemical Sciences, Queen Mary, University of London, London, E1 4NS, UK.
Defects in chromosome-microtubule attachment can cause chromosomal instability (CIN), frequently associated with infertility and aggressive cancers. Chromosome-microtubule attachment is mediated by a large macromolecular structure, the kinetochore. Sister kinetochores of each chromosome are pulled by microtubules from opposing spindle-poles, a state called biorientation which prevents chromosome missegregation.
View Article and Find Full Text PDFJ Cell Sci
August 2018
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
Protein ubiquitylation regulates many cellular processes, including cell division. We report here a novel mutation altering the E1 ubiquitin-activating enzyme () that suppresses the temperature sensitivity and chromosome loss phenotype of a well-characterized Aurora B mutant (). The mutation increases histone H3-S10 phosphorylation in the strain, indicating that acts by increasing Ipl1 activity and/or reducing the opposing protein phosphatase 1 (PP1; Glc7 in ) phosphatase activity.
View Article and Find Full Text PDFG3 (Bethesda)
December 2012
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Ipl1/Aurora B is the catalytic subunit of a protein kinase complex required for chromosome segregation and nuclear division. Before anaphase, Ipl1 is required to establish proper kinetochore-microtubule associations and to regulate the spindle assembly checkpoint (SAC). The phosphatase Glc7/PP1 opposes Ipl1 for these activities.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2011
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
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.
View Article and Find Full Text PDFJ Cell Sci
June 2010
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
The assembly, disassembly and dynamic movement of macromolecules are integral to cell physiology. The ubiquitin-selective chaperone Cdc48 (p97 in Metazoa), an AAA-ATPase, might facilitate such processes in the cell cycle. Cdc48 in budding yeast was initially isolated from a mitotic mutant.
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