Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1–Cdk1 at the centrosome

Lindqvist, Arne; Källström, Helena; Lundgren, A.; Barsoum, Emad; Rosenthal, Christina Karlsson

doi:10.1083/jcb.200503066

Cited by 176 publications

(203 citation statements)

References 56 publications

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“…The localization of cyclin A/cdk2 to the centrosome in late G 2 phase, prior to evidence of microtubule nucleation, suggests that it may normally have a role in regulating the timing of cyclin B/cdk1 activation at that location. Cyclin B/cdk1 is activated at the centrosome by the cdc25B phosphatase (Lindqvist et al, 2005), and Aurora A has been reported to phosphorylate and regulate cdc25B at the centrosome (Dutertre et al, 2004). This Aurora A-dependent mechanism may ensure activation of the centrosomal cyclin B/cdk1 precedes activation of the major soluble pool.…”

Section: Discussionmentioning

confidence: 99%

Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

et al. 2008

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Cyclin A/cdk2 has a role in progression through S phase, and a large pool is also activated in G 2 phase. Here we report that this G 2 phase pool regulates the timing of progression into mitosis. Knock down of cyclin A by siRNA or addition of a specific cdk2 small molecule inhibitor delayed entry into mitosis by delaying cells in G 2 phase. The G 2 phase-delayed cells contained elevated levels of inactive cyclin B/cdk1. However, increased microtubule nucleation at the centrosomes was observed, and the centrosomes stained for markers of cyclin B/cdk1 activity. Both microtubule nucleation at the centrosomes and the phosphoprotein markers were lost with short-term treatment of the cdk1/2 inhibitor roscovitine but not the Mek1/2 inhibitor U0126. Cyclin A/cdk2 localized at the centrosomes in late G 2 phase after separation of the centrosomes but before the start of prophase. Thus G 2 phase cyclin A/cdk2 controls the timing of entry into mitosis by controlling the subsequent activation of cyclin B/cdk1, but also has an unexpected role in coordinating the activation of cyclin B/cdk1 at the centrosome and in the nucleus.

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Section: Discussionmentioning

confidence: 99%

Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

et al. 2008

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“…During interphase, Golgi ribbons are positioned adjacent to, and may be physically linked to, centrosomes actively involved in nucleating microtubule assembly (for reviews, see Rios and Bornens, 2003;Linstedt, 2004). In preparation for mitosis, centrosome duplication and separation are required steps before CDK1 activation (Lindqvist et al, 2005). A linked Golgi apparatus may impede centrosome separation, and this, in turn, might cause a delay in G 2 /M.…”

Section: Mek1-mediated Golgi Unlinkingmentioning

confidence: 99%

Mitogen-activated Protein Kinase Kinase 1-dependent Golgi Unlinking Occurs in G₂Phase and Promotes the G₂/M Cell Cycle Transition

Feinstein

Linstedt

2007

MBoC

101

162

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Two controversies have emerged regarding the signaling pathways that regulate Golgi disassembly at the G2/M cell cycle transition. The first controversy concerns the role of mitogen-activated protein kinase activator mitogen-activated protein kinase kinase (MEK)1, and the second controversy concerns the participation of Golgi structure in a novel cell cycle “checkpoint.” A potential simultaneous resolution is suggested by the hypothesis that MEK1 triggers Golgi unlinking in late G2 to control G2/M kinetics. Here, we show that inhibition of MEK1 by RNA interference or by using the MEK1/2-specific inhibitor U0126 delayed the passage of synchronized HeLa cells into M phase. The MEK1 requirement for normal mitotic entry was abrogated if Golgi proteins were dispersed before M phase by treatment of cells with brefeldin A or if GRASP65, which links Golgi stacks into a ribbon network, was depleted. Imaging revealed that unlinking of the Golgi apparatus begins before M phase, is independent of cyclin-dependent kinase 1 activation, and requires MEK signaling. Furthermore, expression of the GRASP family member GRASP55 after alanine substitution of its MEK1-dependent mitotic phosphorylation sites inhibited both late G2 Golgi unlinking and the G2/M transition. Thus, MEK1 plays an in vivo role in Golgi reorganization, which regulates cell cycle progression.

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“…Centrosomal Cdk1-Cyclin B activation has a role in the process of centrosome separation (Blangy et al, 1997;Jackman et al, 2003;Lindqvist et al, 2005). Interestingly, Kramer et al, determined that Cdk1 is prevented from premature activation by Chk1 at centrosomes (Kramer et al, 2004).…”

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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Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1–Cdk1 at the centrosome

Cited by 176 publications

References 56 publications

Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

Mitogen-activated Protein Kinase Kinase 1-dependent Golgi Unlinking Occurs in G₂Phase and Promotes the G₂/M Cell Cycle Transition

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

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Cdc25B cooperates with Cdc25A to induce mitosis but has a unique role in activating cyclin B1–Cdk1 at the centrosome

Cited by 176 publications

References 56 publications

Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

Cyclin A/cdk2 coordinates centrosomal and nuclear mitotic events

Mitogen-activated Protein Kinase Kinase 1-dependent Golgi Unlinking Occurs in G2Phase and Promotes the G2/M Cell Cycle Transition

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

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Mitogen-activated Protein Kinase Kinase 1-dependent Golgi Unlinking Occurs in G₂Phase and Promotes the G₂/M Cell Cycle Transition