Phosphorylation of Microtubule-binding Protein Hec1 by Mitotic Kinase Aurora B Specifies Spindle Checkpoint Kinase Mps1 Signaling at the Kinetochore

Zhu, Tongge; Dou, Zhen; Qin, Bo; Jin, Changjie; Wang, Xinghui; Xu, Leilei; Wang, Zhaoyang; Zhu, Lijuan; Liu, Fusheng; Gao, Xiaolan; Ke, Youqi; Wang, Zhiyong; Aikhionbare, Felix; Fu, Cuizhang; Ding, Xia; Yao, Xuebiao

doi:10.1074/jbc.m113.507970

Cited by 61 publications

(66 citation statements)

References 50 publications

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“…It is likely that, upon activation, the conformation of Mps1 changes to block the interaction of the IRK with Ndc80C. This blocking then would allow the TPR domain (together with the NTE) to act solely and to bias Mps1 binding to Hec1 in a dynamic manner (21,23). We emphasize that the localization of active Mps1 to the kinetochore is compatible with the incorrect MT attachment (e.g., monastrol treatment; Fig.…”

Section: Mis12cmentioning

confidence: 87%

“…Although the molecular mechanism remains unclear, Mps1 is required to recruit Mad1 and Mad2 to unattached kinetochores, supporting its essential role in SAC activity (15)(16)(17)(18). It also is clear that aurora B kinase activity and the outer-layer kinetochore protein nuclear division cycle 80 (Ndc80)/Hec1 are required for Mps1 localization to kinetochores, as evidenced by recent work, including ours (17,(19)(20)(21)(22)(23)(24). How Mps1 activates the SAC is now becoming clear.…”

mentioning

confidence: 86%

“…How then does the accumulated inactive Mps1 at kinetochores affect chromosome alignment? Because the Hec1 MT-binding domain also is required for recruiting Mps1 to kinetochores (21,23), it is likely that the Hec1-MT binding and Hec1-Mps1 binding are mutually exclusive. In support of this view, our study showed that the kinetochore localization of inactive Mps1, but not active Mps1, prevented the establishment of stable kinetochore-MT attachments.…”

Section: Mis12cmentioning

confidence: 99%

“…The kinetochore localization of Mps1 WT depends on aurora B kinase activity (19,20,22,23). We next asked whether the recruitment of inactive Mps1 to the kinetochore also depends on aurora B.…”

Section: The Localization Of Inactive Mps1 To Unattached Kinetochores Ismentioning

confidence: 99%

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Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Dou

Liu

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.Mps1 kinase | spindle assembly checkpoint | chromosome alignment | kinetochore-microtubule attachment | reversine

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Section: Mis12cmentioning

confidence: 87%

mentioning

confidence: 86%

Section: Mis12cmentioning

confidence: 99%

Section: The Localization Of Inactive Mps1 To Unattached Kinetochores Ismentioning

confidence: 99%

See 2 more Smart Citations

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Dou

Liu

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…To better illustrate the function of the PXVXL-mediated borealin-HP1␣ interaction in chromosome segregation, we next examined the localization of Aurora B in borealin V231E -expressing cells lacking endogenous borealin, which was achieved by expressing shRNA-resistant borealin (32,33). As shown in Fig.…”

Section: Volume 289 • Number 30 • July 25 2014mentioning

confidence: 99%

Chromatin Protein HP1α Interacts with the Mitotic Regulator Borealin Protein and Specifies the Centromere Localization of the Chromosomal Passenger Complex

Liu

Song

Huo

et al. 2014

Journal of Biological Chemistry

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Background: Borealin is a conserved centromere protein essential for mitosis. Results: Borealin interacts with HP1␣, and this interaction recruits the CPC to the centromere. Conclusion: The HP1␣-borealin interaction specifies CPC localization in the centromere. Significance: A physical link between CPC and HP1␣ in the centromere orchestrates chromosome segregation and accurate cell division.

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Orchestration of the spindle assembly checkpoint by CDK1‐cyclin B1

2019

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In mitosis, the spindle assembly checkpoint (SAC) monitors the formation of microtubule‐kinetochore attachments during capture of chromosomes by the mitotic spindle. Spindle assembly is complete once there are no longer any unattached kinetochores. Here, we will discuss the mechanism and key components of spindle checkpoint signalling. Unattached kinetochores bind the principal spindle checkpoint kinase monopolar spindle 1 (MPS1). MPS1 triggers the recruitment of other spindle checkpoint proteins and the formation of a soluble inhibitor of anaphase, thus preventing exit from mitosis. On microtubule attachment, kinetochores become checkpoint silent due to the actions of PP2A‐B56 and PP1. This SAC responsive period has to be coordinated with mitotic spindle formation to ensure timely mitotic exit and accurate chromosome segregation. We focus on the molecular mechanisms by which the SAC permissive state is created, describing a central role for CDK1‐cyclin B1 and its counteracting phosphatase PP2A‐B55. Furthermore, we discuss how CDK1‐cyclin B1, through its interaction with MAD1, acts as an integral component of the SAC, and actively orchestrates checkpoint signalling and thus contributes to the faithful execution of mitosis.

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Phosphorylation of Microtubule-binding Protein Hec1 by Mitotic Kinase Aurora B Specifies Spindle Checkpoint Kinase Mps1 Signaling at the Kinetochore

Cited by 61 publications

References 50 publications

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Dynamic localization of Mps1 kinase to kinetochores is essential for accurate spindle microtubule attachment

Chromatin Protein HP1α Interacts with the Mitotic Regulator Borealin Protein and Specifies the Centromere Localization of the Chromosomal Passenger Complex

Orchestration of the spindle assembly checkpoint by CDK1‐cyclin B1

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