scholarly journals Bistability of mitotic entry and exit switches during open mitosis in mammalian cells

BioEssays ◽  
2016 ◽  
Vol 38 (7) ◽  
pp. 627-643 ◽  
Author(s):  
Nadia Hégarat ◽  
Scott Rata ◽  
Helfrid Hochegger
Keyword(s):  
Mammalian Cells ◽  
Entry And Exit ◽  
Mitotic Entry

scholarly journals MEK1 inactivates Myt1 to regulate Golgi membrane fragmentation and mitotic entry in mammalian cells

2012 ◽  
Vol 32 (1) ◽  
pp. 72-85 ◽  
Author(s):  
Julien Villeneuve ◽  
Margherita Scarpa ◽  
Maria Ortega-Bellido ◽  
Vivek Malhotra
Keyword(s):  
Mammalian Cells ◽  
Golgi Membrane ◽  
Mitotic Entry

scholarly journals The nucleus serves as the pacemaker for the cell cycle

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Oshri Afanzar ◽  
Garrison K Buss ◽  
Tim Stearns ◽  
James E Ferrell
Keyword(s):  
Cell Cycle ◽  
Tubulin Polymerization ◽  
Entry And Exit ◽  
Mitotic Entry ◽  
Cellular Location ◽  
Phage Dna ◽  
Egg Extracts ◽  
The Waves

Mitosis is a dramatic process that affects all parts of the cell. It is driven by an oscillator whose various components are localized in the nucleus, centrosome, and cytoplasm. In principle, the cellular location with the fastest intrinsic rhythm should act as a pacemaker for the process. Here we traced the waves of tubulin polymerization and depolymerization that occur at mitotic entry and exit in Xenopus egg extracts back to their origins. We found that mitosis was commonly initiated at sperm-derived nuclei and their accompanying centrosomes. The cell cycle was ~20% faster at these initiation points than in the slowest regions of the extract. Nuclei produced from phage DNA, which did not possess centrosomes, also acted as trigger wave sources, but purified centrosomes in the absence of nuclei did not. We conclude that the nucleus accelerates mitotic entry and propose that it acts as a pacemaker for cell cycle.

scholarly journals Bistable, biphasic regulation of PP2A-B55 accounts for the dynamics of mitotic substrate phosphorylation

2020 ◽  
Author(s):  
Julia Kamenz ◽  
Lendert Gelens ◽  
James E. Ferrell
Keyword(s):  
Mitotic Exit ◽  
Cyclin Dependent Kinase ◽  
Entry And Exit ◽  
Bistable Switch ◽  
Mitotic Entry ◽  
Low Concentrations ◽  
M Phase ◽  
Egg Extracts ◽  
Substrate Phosphorylation ◽  
High Concentrations

SummaryThe phosphorylation of mitotic proteins is bistable, which contributes to the decisiveness of the transitions into and out of M phase. The bistability in substrate phosphorylation has been attributed to bistability in the activation of the cyclin-dependent kinase Cdk1. However, more recently it has been suggested that bistability also arises from positive feedback in the regulation of the Cdk1-counteracting phosphatase, PP2A-B55. Here, we demonstrate biochemically using Xenopus laevis egg extracts that the Cdk1-counteracting phosphatase PP2A-B55 functions as a bistable switch, even when the bistability of Cdk1 activation is suppressed. In addition, Cdk1 regulates PP2A-B55 in a biphasic manner; low concentrations of Cdk1 activate PP2A-B55 and high concentrations inactivate it. As a consequence of this incoherent feedforward regulation, PP2A-B55 activity rises concurrently with Cdk1 activity during interphase and suppresses substrate phosphorylation. PP2A-B55 activity is then sharply downregulated at the onset of mitosis. During mitotic exit Cdk1 activity initially falls with no obvious change in substrate phosphorylation; dephosphorylation then commences once PP2A-B55 spikes in activity. These findings suggest that changes in Cdk1 activity are permissive for mitotic entry and exit, but the changes in PP2A-B55 activity are the ultimate trigger.

The Golgi ribbon: mechanisms of maintenance and disassembly during the cell cycle

2020 ◽  
Vol 48 (1) ◽  
pp. 245-256 ◽  
Author(s):  
Inmaculada Ayala ◽  
Fabiola Mascanzoni ◽  
Antonino Colanzi
Keyword(s):  
Signaling Pathways ◽  
Mammalian Cells ◽  
Mitotic Entry ◽  
Daughter Cells ◽  
The Core ◽  
Disassembly Process ◽  
Pathological Conditions ◽  
Golgi Structure ◽  
Golgi Ribbon ◽  
Complex Structural

The Golgi complex (GC) has an essential role in the processing and sorting of proteins and lipids. The GC of mammalian cells is composed of stacks of cisternae connected by membranous tubules to create a continuous network, the Golgi ribbon, whose maintenance requires several core and accessory proteins. Despite this complex structural organization, the Golgi apparatus is highly dynamic, and this property becomes particularly evident during mitosis, when the ribbon undergoes a multistep disassembly process that allows its correct partitioning and inheritance by the daughter cells. Importantly, alterations of the Golgi structure are associated with a variety of physiological and pathological conditions. Here, we review the core mechanisms and signaling pathways involved in both the maintenance and disassembly of the Golgi ribbon, and we also report on the signaling pathways that connect the disassembly of the Golgi ribbon to mitotic entry and progression.

scholarly journals SLK-dependent activation of ERMs controls LGN–NuMA localization and spindle orientation

2014 ◽  
Vol 205 (6) ◽  
pp. 791-799 ◽  
Author(s):  
Mickael Machicoane ◽  
Cristina A. de Frutos ◽  
Jenny Fink ◽  
Murielle Rocancourt ◽  
Yannis Lombardi ◽  
...  
Keyword(s):  
Mitotic Spindle ◽  
Mammalian Cells ◽  
Molecular Level ◽  
Spindle Orientation ◽  
Cell Cortex ◽  
Mitotic Apparatus ◽  
Mitotic Entry ◽  
Spindle Microtubules ◽  
Force Generator

Mitotic spindle orientation relies on a complex dialog between the spindle microtubules and the cell cortex, in which F-actin has been recently implicated. Here, we report that the membrane–actin linkers ezrin/radixin/moesin (ERMs) are strongly and directly activated by the Ste20-like kinase at mitotic entry in mammalian cells. Using microfabricated adhesive substrates to control the axis of cell division, we found that the activation of ERMs plays a key role in guiding the orientation of the mitotic spindle. Accordingly, impairing ERM activation in apical progenitors of the mouse embryonic neocortex severely disturbed spindle orientation in vivo. At the molecular level, ERM activation promotes the polarized association at the mitotic cortex of leucine-glycine-asparagine repeat protein (LGN) and nuclear mitotic apparatus (NuMA) protein, two essential factors for spindle orientation. We propose that activated ERMs, together with Gαi, are critical for the correct localization of LGN–NuMA force generator complexes and hence for proper spindle orientation.

scholarly journals Roles of aurora-A kinase in mitotic entry and G2 checkpoint in mammalian cells

2002 ◽  
Vol 7 (11) ◽  
pp. 1173-1182 ◽  
Author(s):  
Tomotoshi Marumoto ◽  
Toru Hirota ◽  
Tetsuro Morisaki ◽  
Naoko Kunitoku ◽  
Dongwei Zhang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Mitotic Entry ◽  
G2 Checkpoint

scholarly journals USP7 couples DNA replication termination to mitotic entry

2018 ◽  
Author(s):  
Antonio Galarreta ◽  
Emilio Lecona ◽  
Pablo Valledor ◽  
Patricia Ubieto ◽  
Vanesa Lafarga ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Chromosome Segregation ◽  
Mechanism Of Action ◽  
Mammalian Cells ◽  
Essential Role ◽  
Premature Termination ◽  
Mitotic Entry ◽  
Entire Cell ◽  
Segregation Of Chromosomes

SUMMARYTo ensure a faithful segregation of chromosomes, DNA must be fully replicated before mitotic entry. However, how cells sense the completion of DNA replication and to what extent this is linked to the activation of the mitotic machinery remains poorly understood. We previously showed that USP7 is a replisome-associated deubiquitinase with an essential role in DNA replication. Here, we reveal that USP7 inhibition leads to the ubiquitination of MCM7, a hallmark of DNA replication termination. In addition, USP7 inhibition leads to the ubiquitination of additional replisome components such as POLD1, which are displaced from replisomes. Surprisingly, this premature termination of DNA replication occurs concomitant to a generalized activation of CDK1 throughout the entire cell cycle, which impairs chromosome segregation and is toxic for mammalian cells. Accordingly, the toxicity of USP7 inhibitors is alleviated by CDK1 inhibition. Our work sheds light into the mechanism of action of USP7 inhibitors and provides evidence to the concept that DNA replication termination is coupled to the activation of the mitotic program.

scholarly journals The Auto-ubiquitylation of E3 Ubiquitin-protein Ligase Chfr at G2Phase Is Required for Accumulation of Polo-like Kinase 1 and Mitotic Entry in Mammalian Cells

2011 ◽  
Vol 286 (35) ◽  
pp. 30615-30623 ◽  
Author(s):  
Jo-Sun Kim ◽  
Yong-Yea Park ◽  
Sun-Yi Park ◽  
Hyeseon Cho ◽  
Dongmin Kang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Mitotic Entry ◽  
Ubiquitin Protein Ligase

scholarly journals Myt1 protein kinase is essential for Golgi and ER assembly during mitotic exit

2008 ◽  
Vol 181 (1) ◽  
pp. 89-103 ◽  
Author(s):  
Hiroyuki Nakajima ◽  
Shigenobu Yonemura ◽  
Masayuki Murata ◽  
Nobuhiro Nakamura ◽  
Helen Piwnica-Worms ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Mammalian Cells ◽  
Cyclin B1 ◽  
Membrane Dynamics ◽  
Mitotic Exit ◽  
Negative Regulator ◽  
Unexpected Finding ◽  
Intracellular Membrane ◽  
Mitotic Entry ◽  
Cdc2 Activity

Myt1 was originally identified as an inhibitory kinase for Cdc2 (Cdk1), the master engine of mitosis, and has been thought to function, together with Wee1, as a negative regulator of mitotic entry. In this study, we report an unexpected finding that Myt1 is essential for Golgi and endoplasmic reticulum (ER) assembly during telophase in mammalian cells. Our analyses reveal that both cyclin B1 and cyclin B2 serve as targets of Myt1 for proper Golgi and ER assembly to occur. Thus, our results show that Myt1-mediated suppression of Cdc2 activity is not indispensable for the regulation of a broad range of mitotic events but is specifically required for the control of intracellular membrane dynamics during mitosis.

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