Getting in and out of mitosis with Polo-like kinase-1

Vugt, Marcel A.T.M. van; Medema, René H.

doi:10.1038/sj.onc.1208617

Cited by 250 publications

(223 citation statements)

References 156 publications

(212 reference statements)

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“…3b, far right images). Thus, as Plk-1 levels and activity are both required for proper centrosomes maturation 19 ; without them, the precise localization of Kin-1 to the vicinity of centrosomes is greatly impaired. As Plk-1 is a critical cell cycle kinase, we next asked whether Kin-1 was a substrate of Plk-1.…”

Section: Resultsmentioning

confidence: 99%

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

et al. 2013

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Kindlin-1 binds to integrins and regulates integrin activation at cell adhesions. Here we report a new function of Kindlin-1 in regulating spindle assembly. We show that Kindlin-1 localizes to centrosomes, its concentration peaking during G2/M, where it associates with various pericentriolar material proteins, including Polo-like kinase 1. Short interfering RNA-mediated depletion of Kindlin-1 increases formation of abnormal mitotic spindles and decreases cellular survival. This effect is dependent not only on the ability of Kindlin-1 to bind integrins but also on Polo-like kinase 1-mediated Kindlin-1 phosphorylation. We demonstrate that a subcellular pool of phosphorylated Kindlin-1 is located exclusively at centrosomes. Our work identifies a novel cellular role for Kindlin-1 in ensuring mitotic spindle assembly and cellular survival that is controlled by phosphorylation via Polo-like kinase 1.

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Section: Resultsmentioning

confidence: 99%

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

et al. 2013

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“…In this mechanism of Cdk1 activation, it is thought that both active Plk1 and Cdk1 prevent Wee1 and Myt1 inhibitory phosphorylations on Cdk1. Adapted from Barr et al, 2004and van Vugt and Medema, 2005(Barr et al, 2004van Vugt and Medema, 2005 Mitosis onset is signified by active Cdk1-Cyclin B translocation from the cytoplasm to the nucleus, which is regulated by a phosphorylation event on Cyclin B Hagting et al, 1999). It is postulated that nuclear translocation is mediated by Plk1 phosphorylation of Cyclin B (Toyoshima-Morimoto et al, 2001;Yuan et al, 2002).…”

Section: Figure 13 Cdk1 Activation Pathwaymentioning

confidence: 99%

“…As well as mitotic entry, active centrosomal Plk1 also functions in the formation of spindle arrays (van Vugt and Medema, 2005;Golsteyn et al, 1995). Early Drosophila melanogaster (Drosophilia) polo-like kinase (gene product polo) mutation studies showed embryos with irregular spindle formation resulting from aberrant centrosomes (Sunkel and Glover, 1988).…”

Section: Figure 13 Cdk1 Activation Pathwaymentioning

confidence: 99%

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Smith¹,

Dejsuphong

Balestrini³

et al. 2009

Nat Cell Biol

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The effects of ATM and ATR signalling induced by chromosomal breakage have been described extensively in modulating cell cycle progression up to the onset of mitosis.However, DNA damage checkpoint responses in mitotic cells are not well understood.This thesis reports on the effects of double strand breaks on the progression of mitosis.We found ATM and ATR activation can occur in mitotic Xenopus laevis egg extract and the induction of ATM and ATR by chromosomal breakages inhibits spindle assembly in both Xenopus egg extract and somatic cells. The delay in mitotic progression induced by ATM and ATR was found not to involve major spindle assembly factors activities such as, Cdk1, Plx1 and RCC1/Ran-GTP. However, normal anastral spindles formation around linear DNA coated beads, which can activate ATM and ATR, linked centrosome-driven spindle assembly to ATM and ATR dependent spindle defects. cDNA expression library screening was undertaken to identify novel ATM and ATR targets in this mitotic checkpoint pathway, through which the novel centrosomal protein XCEP63 was identified as a likely candidate. Data obtained from depletion and reconstitution of XCEP63 in Xenopus egg extract established that normal centrosome-driven spindle assembly requires XCEP63. Moreover, ATM and ATR phosphorylates XCEP63 on serine 560 and promotes delocalisation from the centrosome. ATM and ATR inhibition or addition of non-phosphorylable XCEP63 recombinant protein mutated at serine 560 prevents spindle assembly abnormalities.These findings suggest that ATM and ATR regulate mitotic events by targeting XCEP63 and centrosome-dependent spindle assembly. This pathway may provide support for DNA repair processes or regulate cell survival in the presence of mitotic DNA damage. 3

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“…In mammalian cells, there exists three CDC25 family members (CDC25A-C; for review, see Boutros et al, 2006). It has been demonstrated that CDC25B cooperates with CDC25A to control entry into mitosis (Lindqvist et al, 2005), and is the only CDC25 phosphatase shown to be required for re-entry in mitosis after DNA damage-induced G 2 cell-cycle arrest (van Vugt et al, 2004;van Vugt and Medema, 2005). CDC25B phosphatase activity appears to be highly regulated by phosphorylation mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Differential mitotic degradation of the CDC25B phosphatase variants

et al. 2007

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CDC25 phosphatases control cell-cycle progression by dephosphorylating and activating cyclin-dependent kinases. CDC25B, one of the three members of this family in human cells, is thought to regulate initial mitotic events. CDC25B is an unstable protein whose proteasomal degradation is proposed to be controlled by b-TrCP. Here, we have investigated the regulation of CDC25B during mitosis, using time-lapse video microscopy. We found that CDC25B expression is high during early mitosis, and that its degradation occurs after the metaphase-anaphase transition and cyclin B1 destruction. We also show that CDC25B degradation after metaphase is dependent on the integrity of the KEN-box and RRKSE motifs that are located within the alternatively spliced B domain, and that the CDC25B2 splice variant, that lacks this domain, is stable during mitosis. Furthermore, we show that the N-terminal region of CDC25B, encompassing the B domain, undergoes major conformational changes during mitosis that can be monitored by intramolecular fluorescence resonance energy transfer variation of specific CDC25B biosensors. This study demonstrates that CDC25B splice variants have differential mitotic stabilities, a feature that is likely to have major consequences on the local control of cyclin-dependent kinase-cyclin activities during mitotic progression.

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Getting in and out of mitosis with Polo-like kinase-1

Cited by 250 publications

References 156 publications

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1

An ATM- and ATR-dependent checkpoint inactivates spindle assembly by targeting CEP63

Differential mitotic degradation of the CDC25B phosphatase variants

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