The G2/M checkpoint phosphatase cdc25C is located within centrosomes

Busch, Corinna; Barton, Olivia; Morgenstern, Eberhard; Götz, Claudia; Günther, Jürgen; Noll, Andreas; Montenarh, Mathias

doi:10.1016/j.biocel.2007.04.022

Cited by 11 publications

(9 citation statements)

References 34 publications

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“…Cdc25C localises to centrosomes in G 2 and during mitosis. We reinvestigated the subcellular localisation of Cdc25C in HeLa cells using an antibody raised against a specific C-terminal sequence of Cdc25C (C-20) and found, in agreement with another recent study, 43 that whilst most Cdc25C localises to the cytoplasm in asynchronous cells, a fraction of endogenous Cdc25C localises to centrosomes, co-localising with structures staining for pericentriolar material and γ-tubulin ( Fig. 1A and C).…”

Section: Resultssupporting

confidence: 87%

Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis

Bonnet¹,

Coopman²,

Morris³

2008

Cell Cycle

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In mammalian cells, three Cdc25 phosphatases A, B, C coordinate cell cycle progression through activating dephosphorylation of Cyclin-dependent kinases. Whereas Cdc25B is believed to trigger entry into mitosis, Cdc25C is thought to act at a later stage of mitosis and in the nucleus. We report that a fraction of Cdc25C localises to centrosomes in a cell cycle-dependent fashion, as of late S phase and throughout G(2) and mitosis. Moreover, Cdc25C colocalises with Cyclin B1 at centrosomes in G(2) and in prophase and Fluorescence Recovery after Photobleaching experiments reveal that they are both in dynamic exchange between the centrosome and the cytoplasm. The centrosomal localisation of Cdc25C is essentially mediated by its catalytic C-terminal domain, but does not require catalytic activity. In fact phosphatase-dead and substrate-binding hotspot mutants of Cdc25C accumulate at centrosomes together with phosphoTyr15-Cdk1 and behave as dominant negative forms that impair entry into mitosis. Taken together, our data suggest an unexpected function for Cdc25C at the G(2)/M transition, in dephosphorylation of Cdk1. We propose that Cdc25C may participate in amplification of Cdk1-Cyclin B1 activity following initial activation by Cdc25B, and that this process is initiated at the centrosome, then further propagated throughout the cytoplasm thanks to the dynamic behavior of both Cdc25C and Cyclin B1.

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Section: Resultssupporting

confidence: 87%

Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis

Bonnet¹,

Coopman²,

Morris³

2008

Cell Cycle

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“…In addition, increasing evidence suggests that centrosomes also play roles in regulating various cell signalling pathways including cell cycle regulation and the DNA damage response [17-19]. Numerous cell cycle regulatory molecules have been identified at the centrosomes which are though to function as integration sites of positive and negative pathways to regulate cell cycle progression [17,18,20-25]. A growing number of components of the DNA damage response network, including p53, ATM, ATR, CHK1, CHK2, Rad 51, BRCA1 and BRCA2 have also been localized at the centrosomes supporting a role for centrosomes in the DNA damage response [8,9,26-35].…”

Section: Introductionmentioning

confidence: 99%

Cell cycle-dependent localization of CHK2 at centrosomes during mitosis

et al. 2013

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BackgroundCentrosomes function primarily as microtubule-organizing centres and play a crucial role during mitosis by organizing the bipolar spindle. In addition to this function, centrosomes act as reaction centers where numerous key regulators meet to control cell cycle progression. One of these factors involved in genome stability, the checkpoint kinase CHK2, was shown to localize at centrosomes throughout the cell cycle.ResultsHere, we show that CHK2 only localizes to centrosomes during mitosis. Using wild-type and CHK2−/− HCT116 human colon cancer cells and human osteosarcoma U2OS cells depleted for CHK2 with small hairpin RNAs we show that several CHK2 antibodies are non-specific and cross-react with an unknown centrosomal protein(s) by immunofluorescence. To characterize the localization of CHK2, we generated cells expressing inducible GFP-CHK2 and Flag-CHK2 fusion proteins. We show that CHK2 localizes to the nucleus in interphase cells but that a fraction of CHK2 associates with the centrosomes in a Polo-like kinase 1-dependent manner during mitosis, from early mitotic stages until cytokinesis.ConclusionOur findings demonstrate that a subpopulation of CHK2 localizes at the centrosomes in mitotic cells but not in interphase. These results are consistent with previous reports supporting a role for CHK2 in the bipolar spindle formation and the timely progression of mitosis.

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“…It localizes in the nucleus throughout the cell cycle, during which expression of a particular function of PLK1 depends on its subcellular localization (30,31), whereas the particular localization of PLK1 hinges on binding, through its two Polo boxes, to specific targets available at a given time. PLK1 is targeted to the centrosome and kinetochores in early mitosis by binding to phosphorylated centrosomal CDC25C phosphatase (7,22) and phosphorylated kinetochore-associated Bub1, respectively (17,36). A dramatic relocation of PLK1 from the centrosome and kinetochores to the spindle midzone during the subsequent metaphase-anaphase transition is accomplished by an association of PLK1 with PRC1 and MKLP2; both are phosphorylated by PLK1 to become a target for the Polo boxes in PLK1, which in turn relocalize PLK1 to the spindle midzone (30,45).…”

mentioning

confidence: 99%

Polo-Like Kinase Guides Cytokinesis in Trypanosoma brucei through an Indirect Means

Zhi

Umeyama

et al. 2010

Eukaryot Cell

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Polo-like kinase in Trypanosoma brucei (TbPLK) is confined to the flagellum attachment zone (FAZ) and regulates only cytokinetic initiation. However, it apparently diffuses into the cytoplasm before the translocalization of chromosomal passenger complex (CPC) from the midzone of central spindle to FAZ, which is known to be required for initiating cytokinesis. Synchronized T. brucei procyclic cells treated with a TbPLK inhibitor, GW843682X (GW), in late S phase were found to go through a full cell cycle at a normal pace before being arrested at cytokinetic initiation in the second cycle. However, synchronized cells treated with GW in G 1 phase were arrested at cytokinetic initiation within the first cell cycle, suggesting that inhibition of TbPLK at its emergence blocks cytokinesis within the same cell cycle. To rule out potential off-target effects from GW, TbPLK RNA interference (RNAi) was induced to deplete TbPLK, and the progression of synchronized cells from late S phase was also found to be arrested at cytokinetic initiation within the first cell cycle. Apparently, TbPLK has accomplished its role in guiding cytokinesis before the late S phase, presumably by phosphorylating a certain substrate(s) during S phase, which may play a critical role in initiating the subsequent cytokinesis.

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The G2/M checkpoint phosphatase cdc25C is located within centrosomes

Cited by 11 publications

References 34 publications

Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis

Characterization of centrosomal localization and dynamics of Cdc25C phosphatase in mitosis

Cell cycle-dependent localization of CHK2 at centrosomes during mitosis

Polo-Like Kinase Guides Cytokinesis in Trypanosoma brucei through an Indirect Means

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