Functional analysis of phosphorylation of the mitotic centromere-associated kinesin by Aurora B kinase in human tumor cells.

Abstract	Mitotic centromere-associated kinesin (MCAK) is the best characterized member of the kinesin-13 family and plays important roles in microtubule dynamics during mitosis. Its activity and subcellular localization is tightly regulated by an orchestra of mitotic kinases, such as Aurora B. It is well known that serine 196 of MCAK is the major phosphorylation site of Aurora B in Xenopus leavis extracts and that this phosphorylation regulates its catalytic activity and subcellular localization. In the current study, we have addressed the conserved phosphorylation site serine 192 in human MCAK to characterize its function in more depth in human cancer cells. Our data confirm that S192 is the major phosphorylation site of Aurora B in human MCAK and that this phosphorylation has crucial roles in regulating its catalytic activity and localization at the kinetochore/centromere region in mitosis. Interfering with this phosphorylation leads to a delayed progression through prometa- and metaphase associated with mitotic defects in chromosome alignment and segregation. We show further that MCAK is involved in directional migration and invasion of tumor cells, and interestingly, interference with the S192 phosphorylation affects this capability of MCAK. These data provide the first molecular explanation for clinical observation, where an overexpression of MCAK was associated with lymphatic invasion and lymph node metastasis in gastric and colorectal cancer patients.
Authors	Andreas Ritter, Mourad Sanhaji, Alexandra Friemel, Susanne Roth, Udo Rolle, Frank Louwen, Juping Yuan
Journal	Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 14 Issue 23 Pg. 3755-67 ( 2015) ISSN: 1551-4005 [Electronic] United States
PMID	26148251 (Publication Type: Journal Article)
Chemical References	KIF2C protein, human AURKB protein, human Aurora Kinase B Kinesins
Topics	Aurora Kinase B (metabolism, physiology) Binding Sites Cell Line, Tumor Cell Movement (genetics) HeLa Cells Humans Kinesins (chemistry, physiology) Mitosis (genetics) Neoplasm Invasiveness (genetics) Neoplasm Metastasis (genetics) Phosphorylation Protein Processing, Post-Translational Protein Structure, Tertiary

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