scholarly journals Cyclin-dependent kinase 1-mediated AMPK phosphorylation regulates chromosome alignment and mitotic progression

2019 ◽  
Vol 132 (20) ◽  
pp. jcs236000 ◽  
Author(s):  
Seth Stauffer ◽  
Yongji Zeng ◽  
Montserrat Santos ◽  
Jiuli Zhou ◽  
Yuanhong Chen ◽  
...  
Keyword(s):  
Cyclin Dependent Kinase ◽  
Mitotic Progression ◽  
Ampk Phosphorylation ◽  
Chromosome Alignment

scholarly journals Coordination of Chromosome Alignment and Mitotic Progression Chromosome-Based Ran Signal

Cell Cycle ◽  
2007 ◽  
Vol 6 (15) ◽  
pp. 1886-1895 ◽  
Author(s):  
Hoi Y. Li ◽  
Win Pin Ng ◽  
Wong Chi Hang ◽  
Pablo A. Iglesias ◽  
Yixian Zheng
Keyword(s):  
Mitotic Progression ◽  
Chromosome Alignment

scholarly journals Adducin-1 is essential for mitotic spindle assembly through its interaction with myosin-X

2013 ◽  
Vol 204 (1) ◽  
pp. 19-28 ◽  
Author(s):  
Po-Chao Chan ◽  
Rosaline Y.C. Hsu ◽  
Chih-Wei Liu ◽  
Chien-Chen Lai ◽  
Hong-Chen Chen
Keyword(s):  
Mitotic Spindle ◽  
Spindle Assembly ◽  
Actin Binding ◽  
Cyclin Dependent Kinase ◽  
Mitotic Spindles ◽  
Mitotic Progression ◽  
Filamentous Actin ◽  
Multipolar Spindles ◽  
Mitotic Spindle Assembly ◽  
Myosin X

Mitotic spindles are microtubule-based structures, but increasing evidence indicates that filamentous actin (F-actin) and F-actin–based motors are components of these structures. ADD1 (adducin-1) is an actin-binding protein that has been shown to play important roles in the stabilization of the membrane cortical cytoskeleton and cell–cell adhesions. In this study, we show that ADD1 associates with mitotic spindles and is crucial for proper spindle assembly and mitotic progression. Phosphorylation of ADD1 at Ser12 and Ser355 by cyclin-dependent kinase 1 enables ADD1 to bind to myosin-X (Myo10) and therefore to associate with mitotic spindles. ADD1 depletion resulted in distorted, elongated, and multipolar spindles, accompanied by aberrant chromosomal alignment. Remarkably, the mitotic defects caused by ADD1 depletion were rescued by reexpression of ADD1 but not of an ADD1 mutant defective in Myo10 binding. Together, our findings unveil a novel function for ADD1 in mitotic spindle assembly through its interaction with Myo10.

scholarly journals Dual recognition of chromatin and microtubules by INCENP is important for mitotic progression

2017 ◽  
Vol 216 (4) ◽  
pp. 925-941 ◽  
Author(s):  
Michael S. Wheelock ◽  
David J. Wynne ◽  
Boo Shan Tseng ◽  
Hironori Funabiki
Keyword(s):  
Cell Fate ◽  
Binding Capacity ◽  
Mitotic Checkpoint ◽  
Mitotic Arrest ◽  
Cyclin Dependent Kinase ◽  
Mitotic Progression ◽  
Microtubule Binding ◽  
Chromosomal Passenger ◽  
Α Helix

The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP’s microtubule binding, which is negatively regulated by Cyclin-dependent kinase–mediated phosphorylation of segments flanking the SAH domain. The microtubule-binding capacity of the SAH domain is important for mitotic arrest in conditions of suppressed microtubule dynamics, and the duration of mitotic arrest dictates the probability, but not the timing, of cell death. Although independent targeting of INCENP to microtubules or the kinetochore/centromere promotes the mitotic checkpoint, it is insufficient for a robust mitotic arrest. Altogether, our results demonstrate that dual recognition of chromatin and microtubules by CPC is important for checkpoint maintenance and determination of cell fate in mitosis.

scholarly journals Aurora at the pole and equator: overlapping functions of Aurora kinases in the mitotic spindle

Open Biology ◽  
2013 ◽  
Vol 3 (3) ◽  
pp. 120185 ◽  
Author(s):  
Helfrid Hochegger ◽  
Nadia Hégarat ◽  
Jose B. Pereira-Leal
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Spindle ◽  
Aurora Kinase ◽  
Spindle Pole ◽  
Aurora A ◽  
Mitotic Progression ◽  
Aurora Kinases ◽  
Mitotic Kinases ◽  
Chromosome Alignment ◽  
Spindle Microtubules

The correct assembly and timely disassembly of the mitotic spindle is crucial for the propagation of the genome during cell division. Aurora kinases play a central role in orchestrating bipolar spindle establishment, chromosome alignment and segregation. In most eukaryotes, ranging from amoebas to humans, Aurora activity appears to be required both at the spindle pole and the kinetochore, and these activities are often split between two different Aurora paralogues, termed Aurora A and B. Polar and equatorial functions of Aurora kinases have generally been considered separately, with Aurora A being mostly involved in centrosome dynamics, whereas Aurora B coordinates kinetochore attachment and cytokinesis. However, double inactivation of both Aurora A and B results in a dramatic synergy that abolishes chromosome segregation. This suggests that these two activities jointly coordinate mitotic progression. Accordingly, recent evidence suggests that Aurora A and B work together in both spindle assembly in metaphase and disassembly in anaphase. Here, we provide an outlook on these shared functions of the Auroras, discuss the evolution of this family of mitotic kinases and speculate why Aurora kinase activity may be required at both ends of the spindle microtubules.

scholarly journals Multisite phosphorylation by Cdk1 initiates delayed negative feedback to control mitotic transcription

2021 ◽  
Author(s):  
Jonathan B. Asfaha ◽  
Mihkel Örd ◽  
Mart Loog ◽  
David O. Morgan
Keyword(s):  
Gene Expression ◽  
Negative Feedback ◽  
Transcriptional Activation ◽  
Mitotic Arrest ◽  
Cyclin Dependent Kinase ◽  
Feedback Circuit ◽  
Mitotic Progression ◽  
Transcriptional Program ◽  
Multisite Phosphorylation ◽  
Negative Feedback Circuit

AbstractOrdered phosphorylation of cyclin-dependent kinase (CDK) substrates leads to the sequential transcriptional activation and inhibition of hundreds of cell cycle-regulated genes. We find that Ndd1, an activator of genes required for mitotic progression, is both positively and negatively regulated by CDK activity. CDK activity initially stimulates Ndd1-dependent transcription as cells enter mitosis, but prolonged high CDK activity in a mitotic arrest inhibits transcription. The result is a time-delayed negative feedback circuit that generates a pulse of mitotic gene expression. Our results suggest that high CDK activity catalyzes the formation of multiple weak phosphodegrons on Ndd1, leading to its destabilization. Cyclin specificity and phosphorylation kinetics contribute to the timing of Ndd1 destruction. Failure to degrade Ndd1 in a mitotic arrest leads to elevated mitotic gene expression. We conclude that a combination of positive and negative Ndd1 regulation by CDKs governs the timing and magnitude of the mitotic transcriptional program.

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

2015 ◽  
Vol 112 (33) ◽  
pp. E4546-E4555 ◽  
Author(s):  
Zhen Dou ◽  
Xing Liu ◽  
Wenwen Wang ◽  
Tongge Zhu ◽  
Xinghui Wang ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Tetratricopeptide Repeat ◽  
Mitotic Progression ◽  
Microtubule Attachment ◽  
Spatiotemporal Regulation ◽  
Monopolar Spindle ◽  
Evolutionarily Conserved ◽  
Repeat Domain ◽  
Chromosome Alignment ◽  
Tetratricopeptide Repeat Domain

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.

scholarly journals Control of division and microtubule dynamics in Chlamydomonas by cyclin B/CDKB1 and the anaphase-promoting complex

2021 ◽  
Author(s):  
Frederick Cross ◽  
Kresti Pecani ◽  
Kristi Lieberman ◽  
Natsumi Tajima-Shirasaki ◽  
Masayuki Onishi
Keyword(s):  
Time Lapse ◽  
Microtubule Dynamics ◽  
Cyclin B ◽  
Live Cells ◽  
Cyclin Dependent Kinase ◽  
Anaphase Promoting Complex ◽  
Mitotic Progression ◽  
Time Lapse Microscopy ◽  
Spindle Poles ◽  
Multiple Fission

In yeast and animals, cyclin B binds and activates the cyclin-dependent kinase ('CDK') CDK1 to drive entry into mitosis. We show that CYCB1, the sole cyclin B in Chlamydomonas, activates the plant-specific CDKB1 rather than the CDK1 ortholog CDKA1. Time-lapse microscopy shows that CYCB1 is synthesized before each division in the multiple fission cycle, then is rapidly degraded 3-5 minutes before division occurs. CYCB1 degradation is dependent on the anaphase-promoting complex (APC). Like CYCB1, CDKB1 is not synthesized until late G1; however, CDKB1 is not degraded with each division within the multiple fission cycle. The microtubule plus-end-binding protein EB1 labeled with mNeonGreen (EB1-NG) allowed detection of mitotic events in live cells. The earliest detectable step in mitosis, splitting of polar EB1-NG signal into two foci, likely associated with future spindle poles, was dependent on CYCB1. CYCB1-GFP localized close to these foci immediately before spindle formation. Spindle breakdown, cleavage furrow formation and accumulation of EB1 in the furrow were dependent on the APC. In interphase, rapidly growing microtubules are marked by 'comets' of EB1; comets are absent in the absence of APC function. Thus CYCB1/CDKB1 and the APC mitosis modulate microtubule dynamics while regulating mitotic progression.

scholarly journals Leaving no-one behind: how CENP-E facilitates chromosome alignment

2020 ◽  
Vol 64 (2) ◽  
pp. 313-324 ◽  
Author(s):  
Benjamin Craske ◽  
Julie P.I. Welburn
Keyword(s):  
Motor Activity ◽  
Recent Work ◽  
Transport Mechanism ◽  
Genomic Stability ◽  
Mitotic Progression ◽  
Kinesin Motor ◽  
Independent Manner ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
Microtubule Motor

Abstract Chromosome alignment and biorientation is essential for mitotic progression and genomic stability. Most chromosomes align at the spindle equator in a motor-independent manner. However, a subset of polar kinetochores fail to bi-orient and require a microtubule motor-based transport mechanism to move to the cell equator. Centromere Protein E (CENP-E/KIF10) is a kinesin motor from the Kinesin-7 family, which localizes to unattached kinetochores during mitosis and utilizes plus-end directed microtubule motility to slide mono-oriented chromosomes to the spindle equator. Recent work has revealed how CENP-E cooperates with chromokinesins and dynein to mediate chromosome congression and highlighted its role at aligned chromosomes. Additionally, we have gained new mechanistic insights into the targeting and regulation of CENP-E motor activity at the kinetochore. Here, we will review the function of CENP-E in chromosome congression, the pathways that contribute to CENP-E loading at the kinetochore, and how CENP-E activity is regulated during mitosis.

The GTPase Gem and its partner Kif9 are required for chromosome alignment, spindle length control, and mitotic progression

2012 ◽  
Vol 26 (12) ◽  
pp. 5025-5034 ◽  
Author(s):  
Guillaume Andrieu ◽  
Muriel Quaranta ◽  
Corinne Leprince ◽  
Anastassia Hatzoglou
Keyword(s):  
Mitotic Progression ◽  
Chromosome Alignment

scholarly journals An interaction between myosin-10 and the cell cycle regulator Wee1 links spindle dynamics to mitotic progression in epithelia

2018 ◽  
Vol 217 (3) ◽  
pp. 849-859 ◽  
Author(s):  
Joshua C. Sandquist ◽  
Matthew E. Larson ◽  
Sarah Woolner ◽  
Zhiwei Ding ◽  
William M. Bement
Keyword(s):  
Cell Cycle ◽  
Motor Protein ◽  
Cell Junctions ◽  
Dependent Manner ◽  
Cyclin Dependent Kinase ◽  
Mitotic Progression ◽  
Anaphase Onset ◽  
Spindle Dynamics ◽  
Position And Orientation ◽  
Spindle Position

Anaphase in epithelia typically does not ensue until after spindles have achieved a characteristic position and orientation, but how or even if cells link spindle position to anaphase onset is unknown. Here, we show that myosin-10 (Myo10), a motor protein involved in epithelial spindle dynamics, binds to Wee1, a conserved regulator of cyclin-dependent kinase 1 (Cdk1). Wee1 inhibition accelerates progression through metaphase and disrupts normal spindle dynamics, whereas perturbing Myo10 function delays anaphase onset in a Wee1-dependent manner. Moreover, Myo10 perturbation increases Wee1-mediated inhibitory phosphorylation on Cdk1, which, unexpectedly, concentrates at cell–cell junctions. Based on these and other results, we propose a model in which the Myo10–Wee1 interaction coordinates attainment of spindle position and orientation with anaphase onset.

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