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PLoS One. 2014 Sep 29;9(9):e104723. doi: 10.1371/journal.pone.0104723. eCollection 2014.

Dynamic autophosphorylation of mps1 kinase is required for faithful mitotic progression.

Author information

1
Hefei National Laboratory of Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China; Anhui key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, China.
2
Department of Biochemistry, The University of Hong Kong, Hong Kong, China; HKU-Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China.
3
Hefei National Laboratory of Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China; Anhui key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei, China; School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, China.

Abstract

The spindle assembly checkpoint (SAC) is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression.

PMID:
25265012
PMCID:
PMC4179234
DOI:
10.1371/journal.pone.0104723
[Indexed for MEDLINE]
Free PMC Article

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