Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18

Andersen, Søren

doi:10.1016/s0962-8924(00)01786-4

Cited by 193 publications

(145 citation statements)

References 46 publications

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“…3A). MT stability is highly regulated by various MAPs during the highly polar processes of mitosis and cytokinesis [66,87]. Although our evidence suggests that cyclin G2 expression influences MT stability and regrowth, we do not yet know whether cyclin G2 binds together with PP2A/B' on a scaffolding protein or MAP on MTs.…”

Section: Discussionmentioning

confidence: 90%

“…The number of known MAPs has increased and now includes numerous plus-end binding/ tracking proteins and motor proteins with microtubule stabilizing and destabilizing activity [66,88]. Information on how some of these proteins regulate microtubule stability and dynamics is beginning to emerge, though very little is known about the regulation of these new classes of MAPs themselves, including the signaling proteins and enzymes that are involved.…”

Section: Discussionmentioning

confidence: 99%

“…1 and 9). The aberrant MT structures were suggestive of the stabilized MT polymer bundles observed upon ectopic expression of MT associated proteins (MAPs) [65,66]. To test the hypothesis that high cyclin G2 expression influences MT stability, we examined the effect of ectopic G2 expression on the sensitivity of MTs to the MT disrupting agent, nocodazole.…”

Section: Ectopic Cyclin G2 Expression Alters Microtubule Stability Anmentioning

confidence: 99%

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Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

Don

Dallapiazza

Bennin

et al. 2006

Experimental Cell Research

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Cyclin G2 is an atypical cyclin that associates with active protein phosphatase 2A. Cyclin G2 gene expression correlates with cell cycle inhibition; it is significantly upregulated in response to DNA damage and diverse growth inhibitory stimuli, but repressed by mitogenic signals. Ectopic expression of cyclin G2 promotes cell cycle arrest, cyclin dependent kinase 2 inhibition, and the formation of aberrant nuclei [1]. Here we report that endogenous cyclin G2 copurifies with centrosomes and microtubules (MT), and that ectopic G2 expression alters microtubule stability. We find exogenous and endogenous cyclin G2 present at microtubule organizing centers (MTOCs) where it colocalizes with centrosomal markers in a variety of cell lines. We previously reported that cyclin G2 forms complexes with active protein phosphatase 2A (PP2A) and colocalizes with PP2A in a detergent resistant compartment. We now show that cyclin G2 and PP2A colocalize at MTOCs in transfected cells, and that the endogenous proteins copurify with isolated centrosomes. Displacement of the endogenous centrosomal scaffolding protein AKAP450 that anchors PP2A at the centrosome, resulted in the depletion of centrosomal cyclin G2. We find that ectopic expression of cyclin G2 induces microtubule bundling and resistance to depolymerization, inhibition of polymer regrowth from MTOCs, and a p53 dependent cell cycle arrest. Furthermore, we determined that a 100 amino acid carboxy-terminal region of cyclin G2 is sufficient to both direct GFP localization to centrosomes and induce cell cycle inhibition. Colocalization of endogenous cyclin G2 with only one of two GFPcentrin tagged centrioles, the mature centriole present at microtubule foci, indicate that cyclin G2 resides primarily on the mother centriole. Copurification of cyclin G2 and PP2A subunits with microtubules and centrosomes, together with the effects of ectopic cyclin G2 on cell cycle progression, nuclear morphology, and microtubule growth and stability, suggests that cyclin G2 may modulate the cell cycle and cellular division processes through modulation of PP2A and centrosomal associated activities.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Ectopic Cyclin G2 Expression Alters Microtubule Stability Anmentioning

confidence: 99%

See 1 more Smart Citation

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

Don

Dallapiazza

Bennin

et al. 2006

Experimental Cell Research

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“…So far the precise mechanisms that regulate the rapid process of spindle assembly are unclear. In recent years a growing number of studies have underscored the important role of tubulin associated proteins in spindle dynamics, especially those of microtubule associated proteins (MAPs), catastrophe factors (reviewed in Andersen, 2000) and motor proteins (reviewed in Mountain and Compton, 2000). The comprehensive e ects of IC261 on spindle architecture before cells reach the metaphase border point to IC261 directly in¯uencing spindle dynamics.…”

Section: Discussionmentioning

confidence: 99%

IC261, a specific inhibitor of the protein kinases casein kinase 1-delta and -epsilon, triggers the mitotic checkpoint and induces p53-dependent postmitotic effects

et al. 2000

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The p53-targeted kinases casein kinase 1d (CK1d) and casein kinase 1e (CK1e) have been proposed to be involved in regulating DNA repair and chromosomal segregation. Recently, we showed that CK1d localizes to the spindle apparatus and the centrosomes in cells with mitotic failure caused by DNA-damage prior to mitotic entry. We provide here evidence that 3-[(2,4,6-trimethoxyphenyl)methylidenyl]-indolin-2-one (IC261), a novel inhibitor of CK1d and CK1e, triggers the mitotic checkpoint control. At low micromolar concentrations IC261 inhibits cytokinesis causing a transient mitotic arrest. Cells containing active p53 arrest in the postmitotic G1 phase by blockage of entry into the S phase. Cells with non-functional p53 undergo postmitotic replication developing an 8N DNA content. The increase of DNA content is accompanied by a high amount of micronucleated and apoptotic cells. Immun¯uorescence images show that at low concentrations IC261 leads to centrosome ampli®cation causing multipolar mitosis. Our data are consistent with a role for CK1d and CK1e isoforms in regulating key aspects of cell division, possibly through the regulation of centrosome or spindle function during mitosis. Oncogene (2000) 19, 5303 ± 5313.

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“…The spindle microtubule architecture is also governed by microtubule-associated proteins (MAPs), including motor [7] and non-motor MAPs [8] at the spindle poles and kinetochores and along spindle microtubules, which modulate spindle microtubule organization spatially and temporally to determine spindle morphology. The spindle pole proteins NuMA [9] and TPX2 [10] focus the spindle microtubule minus end, while microtubule-dependent motor proteins Eg5 [11], MCAK [12] and the dynein complex [9] generate motor force in the microtubule and transport mitotic proteins to ensure spindle assembly.…”

Section: Introductionmentioning

confidence: 99%

Cep57, a NEDD1-binding pericentriolar material component, is essential for spindle pole integrity

Zhou

et al. 2012

Cell Res

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Formation of a bipolar spindle is indispensable for faithful chromosome segregation and cell division. Spindle integrity is largely dependent on the centrosome and the microtubule network. Centrosome protein Cep57 can bundle microtubules in mammalian cells. Its related protein (Cep57R) in Xenopus was characterized as a stabilization factor for microtubule-kinetochore attachment. Here we show that Cep57 is a pericentriolar material (PCM) component. Its interaction with NEDD1 is necessary for the centrosome localization of Cep57. Depletion of Cep57 leads to unaligned chromosomes and a multipolar spindle, which is induced by PCM fragmentation. In the absence of Cep57, centrosome microtubule array assembly activity is weakened, and the spindle length and microtubule density decrease. As a spindle microtubule-binding protein, Cep57 is also responsible for the proper organization of the spindle microtubule and localization of spindle pole focusing proteins. Collectively, these results suggest that Cep57, as a NEDD1-binding centrosome component, could function as a spindle pole-and microtubule-stabilizing factor for establishing robust spindle architecture.

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Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18

Cited by 193 publications

References 46 publications

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

IC261, a specific inhibitor of the protein kinases casein kinase 1-delta and -epsilon, triggers the mitotic checkpoint and induces p53-dependent postmitotic effects

Cep57, a NEDD1-binding pericentriolar material component, is essential for spindle pole integrity

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