PMID:24187132

Citation	Zhu, T, Dou, Z, Qin, B, Jin, C, Wang, X, Xu, L, Wang, Z, Zhu, L, Liu, F, Gao, X, Ke, Y, Wang, Z, Aikhionbare, F, Fu, C, Ding, X and Yao, X (2013) Phosphorylation of microtubule-binding protein Hec1 by mitotic kinase Aurora B specifies spindle checkpoint kinase Mps1 signaling at the kinetochore. J. Biol. Chem. 288:36149-59
Abstract	The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis.
Links	PubMed PMC3861662 Online version:10.1074/jbc.M113.507970
Keywords	Aurora Kinase B/metabolism; Cell Cycle Checkpoints; Cell Cycle Proteins/metabolism; Gene Expression Regulation; HeLa Cells; Humans; Kinetochores/metabolism; M Phase Cell Cycle Checkpoints; Microtubules/metabolism; Nuclear Proteins/chemistry; Nuclear Proteins/metabolism; Phosphorylation; Protein Structure, Tertiary; Protein Transport; Protein-Serine-Threonine Kinases/metabolism; Protein-Tyrosine Kinases/metabolism; Signal Transduction
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ARATH:HEC1		GO:0006351: transcription, DNA-templated	ECO:0000314:		P		Figure 2 shows that Aurora B phosphorylates the Hec1-N-terminal tail. This phosphorylation causes the regulation of the kinetochore localization of Mps1.	complete CACAO 11823

References

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