Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression

Wang, Peng; Galán, Jacob A.; Normandin, Karine; Bonneil, Éric; Hickson, Gilles R.X.; Roux, Philippe P.; Thibault, Pierre; Archambault, Vincent

doi:10.1083/jcb.201211141

Cited by 39 publications

(77 citation statements)

References 50 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 Celcontrasting

confidence: 52%

“…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: 73%

“…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%

“…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. The NLS of human Gwl was found around KR444/445, 20 the corresponding residues of KR456/457 in Xenopus Gwl.…”

Section: 29mentioning

confidence: 99%

“…[11][12][13] It has also been shown that Gwl can be phosphorylated by Plk1, whereas the specific function and regulation of this modification remains to be further clarified. 11,[13][14][15] In the search for new regulators of Gwl, our proteomic analysis revealed 2 groups of proteins as the major binding partners of Gwl which were co-purified with Gwl from G2 and M phase Xenopus oocytes. Specifically, Gwl bound both the chaperone complex Hsp90/Cdc37 and importin a/b through its N-terminus.…”

Section: Introductionmentioning

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 Celcontrasting

confidence: 52%

Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celmentioning

confidence: 73%

Section: Dynamic Nucleocytoplasmic Localization Of Gwl During the Celmentioning

confidence: 99%

Section: 29mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of Greatwall kinase by protein stabilization and nuclear localization

et al. 2014

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Preparing a cell for nuclear envelope breakdown: Spatio‐temporal control of phosphorylation during mitotic entry

Álvarez-Fernández

Malumbres

2014

BioEssays

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Chromosome segregation requires the ordered separation of the newly replicated chromosomes between the two daughter cells. In most cells, this requires nuclear envelope (NE) disassembly during mitotic entry and its reformation at mitotic exit. Nuclear envelope breakdown (NEB) results in the mixture of two cellular compartments. This process is controlled through phosphorylation of multiple targets by cyclin-dependent kinase 1 (Cdk1)-cyclin B complexes as well as other mitotic enzymes. Experimental evidence also suggests that nucleo-cytoplasmic transport of critical cell cycle regulators such as Cdk1-cyclin B complexes or Greatwall, a kinase responsible for the inactivation of PP2A phosphatases, plays a major role in maintaining the boost of mitotic phosphorylation thus preventing the potential mitotic collapse derived from NEB. These data suggest the relevance of nucleo-cytoplasmic transport not only to communicate cytoplasmic and nuclear compartments during interphase, but also to prepare cells for the mixture of these two compartments during mitosis.

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The Greatwall–PP2A Axis in Cell Cycle Control

Wang

Malumbres

Archambault

2014

Methods in Molecular Biology

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Cell cycle progression is largely controlled by reversible protein phosphorylation mediated by cyclically activated kinases and phosphatases. It has long been known that cyclin B-Cdk1 activation triggers mitotic entry, and the enzymatic network controlling its activation and inactivation has been well characterized. Much more recently protein phosphatase 2A (PP2A) together with its B55 regulatory subunit has been recognized as the major activity dephosphorylating Cdk1 targets. Moreover, PP2A-B55 activity is high in late M phase and interphase, but low at mitotic entry. A series of discoveries in the fly and frog model systems have uncovered the molecular mechanism mediating this regulation. The Greatwall (Gwl) kinase activates endosulfines, which become specific inhibitors of PP2A-B55. Cdk1-dependent activation of Gwl at mitotic entry leads to PP2A-B55 downregulation, which synergizes with Cdk1 activation to promote the phosphorylated states of several mitotic substrates. Much less is known on the mechanisms inactivating Gwl and endosulfines at mitotic exit. Recent reports show the importance of spatiotemporal regulation of Gwl, endosulfines, and PP2A-B55 for cell cycle progression. The various systems and cell types differ in their dependence on the Gwl-PP2A axis for cell cycle progression. Moreover, this pathway also regulates gene expression in yeast, and this function could be conserved in metazoans.

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Cell cycle regulation of Greatwall kinase nuclear localization facilitates mitotic progression

Abstract: Greatwall kinase relocation from the nucleus to the cytoplasm is required at mitotic entry and is mediated by a phosphorylation-dependent mechanism targeting its central region.

Cited by 39 publications

References 50 publications

Regulation of Greatwall kinase by protein stabilization and nuclear localization

Regulation of Greatwall kinase by protein stabilization and nuclear localization

Preparing a cell for nuclear envelope breakdown: Spatio‐temporal control of phosphorylation during mitotic entry

The Greatwall–PP2A Axis in Cell Cycle Control

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