title: Phosphorylation of microtubule-binding protein Hec1 by mitotic kinase Aurora B specifies spindle checkpoint kinase Mps1 signaling at the kinetochore.
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.
authors.affiliation: From the Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230026, China.
authors.forename: Tongge
authors.initials: T
authors.lastname: Zhu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
authors.forename: Bo
authors.initials: B
authors.lastname: Qin
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.forename: Xinghui
authors.initials: X
authors.lastname: Wang
authors.forename: Leilei
authors.initials: L
authors.lastname: Xu
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Wang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhu
authors.forename: Fusheng
authors.initials: F
authors.lastname: Liu
authors.forename: Xinjiao
authors.initials: X
authors.lastname: Gao
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Ke
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
authors.forename: Felix
authors.initials: F
authors.lastname: Aikhionbare
authors.forename: Chuanhai
authors.initials: C
authors.lastname: Fu
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D008870:Microtubules / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human
keywords: Cenp-e; Checkpoint; Checkpoint Control; Kinetochore; Mitosis; Mitotic Spindle; Phosphorylation