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Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos

Tavernier, Nicolas
Martino, Lisa
Van Hove, Lucie
Léger, Thibaut
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Published in The Journal of Cell Biology. 2015, vol. 208, no. 6, p. 661-9
Abstract The molecular mechanisms governing mitotic entry during animal development are incompletely understood. Here, we show that the mitotic kinase CDK-1 phosphorylates Suppressor of Par-Two 1 (SPAT-1)/Bora to regulate its interaction with PLK-1 and to trigger mitotic entry in early Caenorhabditis elegans embryos. Embryos expressing a SPAT-1 version that is nonphosphorylatable by CDK-1 and that is defective in PLK-1 binding in vitro present delays in mitotic entry, mimicking embryos lacking SPAT-1 or PLK-1 functions. We further show that phospho-SPAT-1 activates PLK-1 by triggering phosphorylation on its activator T loop in vitro by Aurora A. Likewise, we show that phosphorylation of human Bora by Cdk1 promotes phosphorylation of human Plk1 by Aurora A, suggesting that this mechanism is conserved in humans. Our results suggest that CDK-1 activates PLK-1 via SPAT-1 phosphorylation to promote entry into mitosis. We propose the existence of a positive feedback loop that connects Cdk1 and Plk1 activation to ensure a robust control of mitotic entry and cell division timing.
Keywords Amino Acid SequenceAnimalsAurora Kinase A/metabolismCDC2 Protein Kinase/physiologyCaenorhabditis elegans/cytology/enzymologyCaenorhabditis elegans Proteins/metabolismCell Cycle Proteins/metabolismEmbryo, Nonmammalian/cytology/metabolismEnzyme ActivationHumansLarva/cytology/enzymologyMitosisMolecular Sequence DataPhosphorylationProtein Processing, Post-TranslationalProtein-Serine-Threonine Kinases/metabolismSf9 CellsSpodoptera
PMID: 25753036
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Article (Published version) (2.1 MB) - public document Free access
Research group La division asymétrique (847)
Projects FNS: 31003A 156013
FNS: 31003A 138501
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TAVERNIER, Nicolas et al. Cdk1 phosphorylates SPAT-1/Bora to trigger PLK-1 activation and drive mitotic entry in C. elegans embryos. In: The Journal of Cell Biology, 2015, vol. 208, n° 6, p. 661-9. https://archive-ouverte.unige.ch/unige:84024

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Deposited on : 2016-05-31

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