Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals

Álvarez-Fernández, Mónica; Martínez, Rubén; Sanz-Castillo, Belén; Gan, Pei Pei; Sanz‐Flores, María; Trakala, Marianna; Ruiz‐Torres, Miguel; Lorca, Thierry; Castro, Anna; Malumbres, Marcos

doi:10.1073/pnas.1310745110

Cited by 102 publications

(190 citation statements)

References 27 publications

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“…This finding is in agreement with previous studies in human and Drosophila that reported nuclear export of Gwl before nuclear membrane breakdown. 15,20 However, distinct from the previous study that suggested a requirement of Gwl kinase activity for its nuclear export, 20 we found a similar pattern of nucleocytoplasmic relocalization for G41S Gwl prior to mitotic entry (Fig. 4B).…”

Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celsupporting

(Expert classified)

“…15,20 We also observed in Xenopus cells that nuclear Gwl started to diffuse into cytoplasm before centrosomes reached opposite positions. While it remained unclear how this nucleocytoplasmic translocation of Gwl may contribute to the regulation of mitotic entry, previous studies indicated that the translocation was dependent on Gwl phosphorylation by CDK1, and possibly also Plk1.…”

Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celmentioning

confidence: 63%

“…15 However, neither of these NLS motifs in Drosophila is conserved in vertebrates. The NLS of human Gwl was found around KR444/445, 20 the corresponding residues of KR456/457 in Xenopus Gwl. Thus, the NLS of Xenopus Gwl, as identified in this study, represents a well-conserved mechanism in vertebrate animals.…”

Section: 29mentioning

confidence: 92%

“…15,20 The Drosophila homolog of Gwl contains 2 essential NLS motifs within the central region, mutation of which disrupted its nuclear location. 15 However, neither of these NLS motifs in Drosophila is conserved in vertebrates.…”

Section: 29mentioning

confidence: 99%

“…While it remained unclear how this nucleocytoplasmic translocation of Gwl may contribute to the regulation of mitotic entry, previous studies indicated that the translocation was dependent on Gwl phosphorylation by CDK1, and possibly also Plk1. 15,20 It was also suggested that the kinase activity of Gwl was required for its nuclear export as a kinasedead form of Gwl harboring a mutation at the ATP-binding site was deficient in nuclear export. 20 However, a different form of kinase-dead Gwl used in our study exhibited a similar pattern of nucleocytoplasmic translocation as the WT.…”

Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celmentioning

confidence: 99%

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Regulation of Greatwall kinase by protein stabilization and nuclear localization

et al. 2014

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Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celsupporting

(Expert classified)

Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celmentioning

confidence: 63%

Section: 29mentioning

confidence: 92%

Section: 29mentioning

confidence: 99%

Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celmentioning

confidence: 99%

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Regulation of Greatwall kinase by protein stabilization and nuclear localization

et al. 2014

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Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A

2019

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Here, we will review the evidence showing that mitotic exit is initiated by regulated proteolysis and then driven by the PPP family of phosphoserine/threonine phosphatases. Rapid APC/CCDC20 and ubiquitin‐dependent proteolysis of cyclin B and securin initiates sister chromatid separation, the first step of mitotic exit. Because proteolysis of Aurora and Polo family kinases dependent on APC/CCDH1 is relatively slow, this creates a new regulatory state, anaphase, different to G2 and M‐phase. We will discuss how the CDK1‐counteracting phosphatases PP1 and PP2A‐B55, together with Aurora and Polo kinases, contribute to the temporal regulation and order of events in the different stages of mitotic exit from anaphase to cytokinesis. For PP2A‐B55, these timing properties are created by the ENSA‐dependent inhibitory pathway and differential recognition of phosphoserine and phosphothreonine. Finally, we will discuss how Aurora B and PP2A‐B56 are needed for the spatial regulation of anaphase spindle formation and how APC/C‐dependent destruction of PLK1 acts as a timer for abscission, the final event of cytokinesis.

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Triggering mitosis

Crncec

Hochegger

2019

FEBS Letters

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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?

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Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals

Cited by 102 publications

References 27 publications

Regulation of Greatwall kinase by protein stabilization and nuclear localization

Regulation of Greatwall kinase by protein stabilization and nuclear localization

Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A

Triggering mitosis

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