title: Dynamic autophosphorylation of mps1 kinase is required for faithful mitotic progression.
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.
authors.affiliation: 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.
authors.forename: Xinghui
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Leilei
authors.initials: L
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Tongge
authors.initials: T
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Fan
authors.initials: F
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D013912:Threonine; D012694:Serine; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human