Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G2–M transition

Dutertre, Stéphanie; Cazalès, Martine; Quaranta, Muriel; Froment, Carine; Trabut, Valerie; Dozier, Christine; Mirey, Gladys; Bouché, Jean‐Pierre; Theis-Febvre, Nathalie; Schmitt, Estelle; Monsarrat, Bernard; Prigent, Claude; Ducommun, Bernard

doi:10.1242/jcs.01108

Cited by 231 publications

(231 citation statements)

References 46 publications

(31 reference statements)

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“…CDC25B is considered to be an unstable protein specifically required for early mitotic events, in particular those occurring at the centrosome level (Gabrielli et al, 1996;Dutertre et al, 2004). The data we present here indicates that this is probably to be only a partial view of CDC25B function.…”

Section: Discussionsupporting

confidence: 45%

“…CDC25B phosphatase activity appears to be highly regulated by phosphorylation mechanisms. A number of regulatory kinases that activate or inhibit CDC25B have been identified (Baldin et al, 1997a(Baldin et al, , 2003Bulavin et al, 2002;Theis-Febvre et al, 2003;Dutertre et al, 2004;Cazales et al 2005;Manke et al, 2005;Mirey et al, 2005;Lemaire et al, 2006;Schmitt et al, 2006) (our unpublished data). These phosphorylation events modulate the catalytic activity, the interactions with regulatory partners such as 14-3-3 proteins, the localization and probably also the stability of CDC25B.…”

Section: Introductionmentioning

confidence: 90%

“…DNA was visualized using diamidino-2-phenylindole. CDC25B rabbit polyclonal antibody (SE4198) against the B domain was described previously (Dutertre et al, 2004). Cyclin B1 monoclonal antibody (GNS1) was purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA).…”

Section: Antibodies and Immunofluorescencementioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 45%

Section: Introductionmentioning

confidence: 90%

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Differential mitotic degradation of the CDC25B phosphatase variants

et al. 2007

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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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“…Additionally, while silencing of Aurora A has been reported to cause delay or block in mitotic entry (Marumoto et al, 2002;Hirota et al, 2003;Du and Hannon, 2004;Satinover et al, 2006), accelerated initiation of mitosis in presence of active Aurora A has also been observed (Ma et al, 2003;Liu and Ruderman, 2006). These effects may, in part, be explained by the reported role of Aurora A in facilitating expression and activation of critical mitosis regulators cyclin B and Cdc25B (Mendez et al, 2000;Tay et al, 2000;Dutertre et al, 2004). However, involvement of Aurora A in regulating specific cellular phenotypes still remain uncertain in view of the inherent limitations in assessing the contributions of the endogenous proteins in ex vivo experiments and also due to occasional contradictory results published on the consequence of ablating Aurora A function in cells grown in vitro (Girdler et al, 2006;Hoar et al, 2007).…”

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confidence: 99%