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Cell Rep. 2015 Jul 7;12(1):58-65. doi: 10.1016/j.celrep.2015.05.039. Epub 2015 Jun 25.

Natural Loss of Mps1 Kinase in Nematodes Uncovers a Role for Polo-like Kinase 1 in Spindle Checkpoint Initiation.

Author information

1
CRBM, CNRS, University of Montpellier, 1919 route de Mende, 34090 Montpellier, France.
2
Laboratory of Chromosome Biology, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
3
Small Molecule Discovery Program, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
4
Laboratory of Chromosome Biology, Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address: abdesai@ucsd.edu.
5
CRBM, CNRS, University of Montpellier, 1919 route de Mende, 34090 Montpellier, France. Electronic address: ariane.abrieu@crbm.cnrs.fr.

Abstract

The spindle checkpoint safeguards against chromosome loss during cell division by preventing anaphase onset until all chromosomes are attached to spindle microtubules. Checkpoint signal is generated at kinetochores, the primary attachment site on chromosomes for spindle microtubules. Mps1 kinase initiates checkpoint signaling by phosphorylating the kinetochore-localized scaffold protein Knl1 to create phospho-docking sites for Bub1/Bub3. Mps1 is widely conserved but is surprisingly absent in many nematode species. Here, we show that PLK-1, which targets a substrate motif similar to that of Mps1, functionally substitutes for Mps1 in C. elegans by phosphorylating KNL-1 to direct BUB-1/BUB-3 kinetochore recruitment. This finding led us to re-examine checkpoint initiation in human cells, where we found that Plk1 co-inhibition significantly reduced Knl1 phosphorylation and Bub1 kinetochore recruitment relative to Mps1 inhibition alone. Thus, the finding that PLK-1 functionally substitutes for Mps1 in checkpoint initiation in C. elegans uncovered a role for Plk1 in species that have Mps1.

PMID:
26119738
PMCID:
PMC4668945
DOI:
10.1016/j.celrep.2015.05.039
[Indexed for MEDLINE]
Free PMC Article

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