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Cdk1-dependent Phosphorylation of KIF4A at S1186 Triggers Lateral Chromosome Compaction During Early Mitosis

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Journal PLoS One
Date 2018 Dec 22
PMID 30576375
Citations 6
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Abstract

Chromosome organization during cell division is achieved through the timely association of proteins with chromatin and is regulated by protein phosphorylation. Kinesin family member 4A (KIF4A) plays an important role in the chromosome organization through the formation of the chromosome scaffold structure. However, the relationship between the function of KIF4A and its phosphorylation remains unclear. Here, we demonstrate that Cdk1-dependent phosphorylation of KIF4A at S1186 is required for chromosome binding and chromosome scaffold formation. The KIF4A mutant, which is not phosphorylated at S1186, was found to localize to the nucleus during interphase but did not accumulate in the chromosome scaffold after nuclear envelope breakdown. In addition, defects in KIF4A phosphorylation were found to disrupt the interaction of KIF4A with the condensin I complex. As a result, the morphology of the chromosomes was observed to be laterally decondensed, without condensin I in the chromosome scaffold. Additionally, a defect in chromosome segregation, chromosome bridge formation, was often observed. Although both KIF4A and condensin I disappeared from the chromosomes, the chromosomal localization of condensin II was not affected. Collectively, our novel results revealed that Cdk1-dependent KIF4A phosphorylation at S1186 is a trigger for chromosomal organization during early mitosis.

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References
1.
Takata H, Uchiyama S, Nakamura N, Nakashima S, Kobayashi S, Sone T . A comparative proteome analysis of human metaphase chromosomes isolated from two different cell lines reveals a set of conserved chromosome-associated proteins. Genes Cells. 2007; 12(3):269-84. DOI: 10.1111/j.1365-2443.2007.01051.x. View

2.
Ohta S, Kimura M, Takagi S, Toramoto I, Ishihama Y . Identification of Mitosis-Specific Phosphorylation in Mitotic Chromosome-Associated Proteins. J Proteome Res. 2016; 15(9):3331-41. DOI: 10.1021/acs.jproteome.6b00512. View

3.
Dong Z, Zhu C, Zhan Q, Jiang W . Cdk phosphorylation licenses Kif4A chromosome localization required for early mitotic progression. J Mol Cell Biol. 2018; 10(4):358-370. DOI: 10.1093/jmcb/mjy033. View

4.
Tada K, Susumu H, Sakuno T, Watanabe Y . Condensin association with histone H2A shapes mitotic chromosomes. Nature. 2011; 474(7352):477-83. DOI: 10.1038/nature10179. View

5.
Kagami Y, Nihira K, Wada S, Ono M, Honda M, Yoshida K . Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis. J Cell Biol. 2014; 205(6):781-90. PMC: 4068140. DOI: 10.1083/jcb.201308172. View