Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis

Joukov, Vladimir; Nicolo, Arcangela De

doi:10.1126/scisignal.aar4195

Cited by 166 publications

(164 citation statements)

References 440 publications

(782 reference statements)

Supporting

Mentioning

162

Contrasting

Order By: Relevance

“…We will conclude this review with a brief outlook on how and why cancer cells might have changed the G2/M switch system, and how this could be further exploited by therapeutic intervention. For other aspects of mitotic entry dynamics, such as spatial regulation and functions of other mitotic kinases, the reader is referred to excellent recent reviews .…”

Section: The Mitotic Trigger Is An Irreversible Cellular Switchmentioning

confidence: 99%

Triggering mitosis

Crncec

Hochegger

2019

FEBS Letters

View full text Add to dashboard Cite

Entry into mitosis is triggered by the activation of cyclin‐dependent kinase 1 (Cdk1). This simple reaction rapidly and irreversibly sets the cell up for division. Even though the core step in triggering mitosis is so simple, the regulation of this cellular switch is highly complex, involving a large number of interconnected signalling cascades. We do have a detailed knowledge of most of the components of this network, but only a poor understanding of how they work together to create a precise and robust system that ensures that mitosis is triggered at the right time and in an orderly fashion. In this review, we will give an overview of the literature that describes the Cdk1 activation network and then address questions relating to the systems biology of this switch. How is the timing of the trigger controlled? How is mitosis insulated from interphase? What determines the sequence of events, following the initial trigger of Cdk1 activation? Which elements ensure robustness in the timing and execution of the switch? How has this system been adapted to the high levels of replication stress in cancer cells?

show abstract

Section: The Mitotic Trigger Is An Irreversible Cellular Switchmentioning

confidence: 99%

Triggering mitosis

Crncec

Hochegger

2019

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…Moreover, the N-terminus binds the Aurora-A kinase and mediates its localisation at spindle MTs [14,15]. TPX2 binding also importantly contributes to Aurora-A kinase activation [16][17][18] and stability [19]. The first 43 amino acids of TPX2 have been described as the region required for Aurora-A binding [16] and deletions within this region have been previously shown to impair Aurora-A/TPX2 interaction and TPX2 regulation of Aurora-A [19,20].…”

Section: Introductionmentioning

confidence: 99%

Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit

Naso

Sterbini

Crecca

et al. 2020

Cells

View full text Add to dashboard Cite

The microtubule-associated protein TPX2 is a key mitotic regulator that contributes through distinct pathways to spindle assembly. A well-characterised function of TPX2 is the activation, stabilisation and spindle localisation of the Aurora-A kinase. High levels of TPX2 are reported in tumours and the effects of its overexpression have been investigated in cancer cell lines, while little is known in non-transformed cells. Here we studied TPX2 overexpression in hTERT RPE-1 cells, using either the full length TPX2 or a truncated form unable to bind Aurora-A, to identify effects that are dependent—or independent—on its interaction with the kinase. We observe significant defects in mitotic spindle assembly and progression through mitosis that are more severe when overexpressed TPX2 is able to interact with Aurora-A. Furthermore, we describe a peculiar, and Aurora-A-interaction-independent, phenotype in telophase cells, with aberrantly stable microtubules interfering with nuclear reconstitution and the assembly of a continuous lamin B1 network, resulting in daughter cells displaying doughnut-shaped nuclei. Our results using non-transformed cells thus reveal a previously uncharacterised consequence of abnormally high TPX2 levels on the correct microtubule cytoskeleton remodelling and G1 nuclei reformation, at the mitosis-to-interphase transition.

show abstract

“…Many regulators of cyclin-CDK activity are also direct or indirect targets of cyclin-CDK activity, creating positive feedback loops that ensure that cyclin-CDK activity continues to rise once activated (Hégarat et al, 2016;Lindqvist et al, 2009;Pomerening, 2009). One such regulator is the kinase PLK1, which, apart from activating cyclin-CDK, plays a key role in mitotic entry and progression (Combes et al, 2017;Joukov and De Nicolo, 2018;Pintard and Archambault, 2018). Here we discuss how spiraling cyclin-CDK activities are kept in check and coordinated with genome duplication.…”

Section: Introductionmentioning

confidence: 99%

DNA replication and mitotic entry: A brake model for cell cycle progression

Lemmens

Lindqvist

2019

Journal of Cell Biology

View full text Add to dashboard Cite

The core function of the cell cycle is to duplicate the genome and divide the duplicated DNA into two daughter cells. These processes need to be carefully coordinated, as cell division before DNA replication is complete leads to genome instability and cell death. Recent observations show that DNA replication, far from being only a consequence of cell cycle progression, plays a key role in coordinating cell cycle activities. DNA replication, through checkpoint kinase signaling, restricts the activity of cyclin-dependent kinases (CDKs) that promote cell division. The S/G2 transition is therefore emerging as a crucial regulatory step to determine the timing of mitosis. Here we discuss recent observations that redefine the coupling between DNA replication and cell division and incorporate these insights into an updated cell cycle model for human cells. We propose a cell cycle model based on a single trigger and sequential releases of three molecular brakes that determine the kinetics of CDK activation.

show abstract

Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis

Cited by 166 publications

References 440 publications

Triggering mitosis

Triggering mitosis

Excess TPX2 Interferes with Microtubule Disassembly and Nuclei Reformation at Mitotic Exit

DNA replication and mitotic entry: A brake model for cell cycle progression

Contact Info

Product

Resources

About