scholarly journals The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability

Oncogene ◽  
2008 ◽  
Vol 27 (29) ◽  
pp. 4107-4114 ◽  
Author(s):  
J Du ◽  
X Cai ◽  
J Yao ◽  
X Ding ◽  
Q Wu ◽  
...  
Keyword(s):  
Mitotic Checkpoint ◽  
Checkpoint Kinase ◽  
Microtubule Attachment

scholarly journals DNA Damage-induced Expression of p53 Suppresses Mitotic Checkpoint Kinase hMps1

2006 ◽  
Vol 281 (13) ◽  
pp. 8675-8685 ◽  
Author(s):  
Mandar R. Bhonde ◽  
Marie-Luise Hanski ◽  
Jan Budczies ◽  
Minh Cao ◽  
Bernd Gillissen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Mitotic Checkpoint ◽  
Induced Expression ◽  
Checkpoint Kinase

scholarly journals Integrated genomic analysis identifies the mitotic checkpoint kinase WEE1 as a novel therapeutic target in medulloblastoma

2014 ◽  
Vol 13 (1) ◽  
pp. 72 ◽  
Author(s):  
Peter S Harris ◽  
Sujatha Venkataraman ◽  
Irina Alimova ◽  
Diane K Birks ◽  
Ilango Balakrishnan ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Genomic Analysis ◽  
Mitotic Checkpoint ◽  
Checkpoint Kinase ◽  
Novel Therapeutic

scholarly journals Breast cancer-specific gene 1 interacts with the mitotic checkpoint kinase BubR1

Oncogene ◽  
2003 ◽  
Vol 22 (48) ◽  
pp. 7593-7599 ◽  
Author(s):  
Anu Gupta ◽  
Satoru Inaba ◽  
Oi Kwan Wong ◽  
Guowei Fang ◽  
Jingwen Liu
Keyword(s):  
Breast Cancer ◽  
Mitotic Checkpoint ◽  
Specific Gene ◽  
Checkpoint Kinase

Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells

2001 ◽  
Vol 114 (24) ◽  
pp. 4385-4395 ◽  
Author(s):  
Stephen S. Taylor ◽  
Deema Hussein ◽  
Yunmei Wang ◽  
Sarah Elderkin ◽  
Christopher J. Morrow
Keyword(s):  
Cell Cycle ◽  
Protein Kinases ◽  
Budding Yeast ◽  
Spindle Assembly ◽  
Mitotic Checkpoint ◽  
Spindle Pole ◽  
Cell Cycle Regulators ◽  
Yeast Gene ◽  
Microtubule Attachment ◽  
Spindle Dynamics

BUB1 is a budding yeast gene required to ensure that progression through mitosis is coupled to correct spindle assembly. Two related human protein kinases, Bub1 and BubR1, both localise to kinetochores during mitosis, suggesting that they play a role in delaying anaphase until all chromosomes achieve correct, bipolar attachment to the spindle. However, how the activities of Bub1 and BubR1 are regulated by spindle events and how their activities regulate downstream cell cycle events is not known.To investigate how spindle events regulate Bub1 and BubR1, we characterised their relative localisations during mitosis in the presence and absence of microtubule toxins. In prometaphase cells, both kinases colocalise to the same domain of the kinetochore. However, whereas the localisation of BubR1 at sister kinetochores is symmetrical, localisation of Bub1 is often asymmetrical. This asymmetry is dependent on microtubule attachment, and the kinetochore exhibiting weaker Bub1 staining is typically closer to the nearest spindle pole. In addition, a 30 minute nocodazole treatment dramatically increases the amount of Bub1 localising to kinetochores but has little effect on BubR1. Furthermore, Bub1 levels increase at metaphase kinetochores following loss of tension caused by taxol treatment. Thus, these observations suggest that Bub1 localisation is sensitive to changes in both tension and microtubule attachment.Consistent with this, we also show that Bub1 is rapidly phosphorylated following brief treatments with nocodazole or taxol. In contrast, BubR1 is phosphorylated in the absence of microtubule toxins, and spindle damage has little additional effect. Although these observations indicate that Bub1 and BubR1 respond differently to spindle dynamics, they are part of a common complex during mitosis. We suggest therefore that Bub1 and BubR1 may integrate different ‘spindle assembly signals’ into a single signal which can then be interpreted by downstream cell cycle regulators.

scholarly journals Spindly/CCDC99 Is Required for Efficient Chromosome Congression and Mitotic Checkpoint Regulation

2010 ◽  
Vol 21 (12) ◽  
pp. 1968-1981 ◽  
Author(s):  
Marin Barisic ◽  
Bénédicte Sohm ◽  
Petra Mikolcevic ◽  
Cornelia Wandke ◽  
Veronika Rauch ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cytoplasmic Dynein ◽  
Mitotic Checkpoint ◽  
Deletion Mutants ◽  
Functional Component ◽  
Checkpoint Signaling ◽  
Microtubule Attachment ◽  
Chromosome Congression ◽  
A Cell ◽  
And Control

Spindly recruits a fraction of cytoplasmic dynein to kinetochores for poleward movement of chromosomes and control of mitotic checkpoint signaling. Here we show that human Spindly is a cell cycle–regulated mitotic phosphoprotein that interacts with the Rod/ZW10/Zwilch (RZZ) complex. The kinetochore levels of Spindly are regulated by microtubule attachment and biorientation induced tension. Deletion mutants lacking the N-terminal half of the protein (NΔ253), or the conserved Spindly box (ΔSB), strongly localized to kinetochores and failed to respond to attachment or tension. In addition, these mutants prevented the removal of the RZZ complex and that of MAD2 from bioriented chromosomes and caused cells to arrest at metaphase, showing that RZZ-Spindly has to be removed from kinetochores to terminate mitotic checkpoint signaling. Depletion of Spindly by RNAi, however, caused cells to arrest in prometaphase because of a delay in microtubule attachment. Surprisingly, this defect was alleviated by codepletion of ZW10. Thus, Spindly is not only required for kinetochore localization of dynein but is a functional component of a mechanism that couples dynein-dependent poleward movement of chromosomes to their efficient attachment to microtubules.

scholarly journals A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Zhejian Ji ◽  
Haishan Gao ◽  
Luying Jia ◽  
Bing Li ◽  
Hongtao Yu
Keyword(s):  
Spindle Checkpoint ◽  
Mitotic Checkpoint ◽  
Anaphase Promoting Complex ◽  
Checkpoint Activation ◽  
Checkpoint Signaling ◽  
Microtubule Attachment ◽  
Anaphase Onset ◽  
Phosphorylation Cascade ◽  
Mitotic Checkpoint Complex

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1–Bub3 and BubR1–Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1–Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/CCdc20) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1–Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

scholarly journals A chemical tool box defines mitotic and interphase roles for Mps1 kinase

2010 ◽  
Vol 190 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Weijie Lan ◽  
Don W. Cleveland
Keyword(s):  
Chromosome Segregation ◽  
Kinase Activity ◽  
Mitotic Checkpoint ◽  
Checkpoint Kinase ◽  
Checkpoint Proteins ◽  
Cell Biol ◽  
Chemical Inhibitors ◽  
Mitotic Inhibitors

In this issue, three groups (Hewitt et al. 2010. J. Cell Biol. doi:10.1083/jcb.201002133; Maciejowski et al. 2010. J. Cell Biol. doi:10.1083/jcb.201001050; Santaguida et al. 2010. J. Cell Biol. doi:10.1083/jcb.201001036) use chemical inhibitors to analyze the function of the mitotic checkpoint kinase Mps1. These studies demonstrate that Mps1 kinase activity ensures accurate chromosome segregation through its recruitment to kinetochores of mitotic checkpoint proteins, formation of interphase and mitotic inhibitors of Cdc20, and correction of faulty microtubule attachments.

scholarly journals Degradation of the Human Mitotic Checkpoint Kinase Mps1 Is Cell Cycle-regulated by APC-cCdc20and APC-cCdh1Ubiquitin Ligases

2010 ◽  
Vol 285 (43) ◽  
pp. 32988-32998 ◽  
Author(s):  
Yongping Cui ◽  
Xiaolong Cheng ◽  
Ce Zhang ◽  
Yanyan Zhang ◽  
Shujing Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mitotic Checkpoint ◽  
Checkpoint Kinase
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