Post‐karyokinesis centrosome movement leaves a trail of unanswered questions

Ou, Young Y.; Rattner, J. B.

doi:10.1002/cm.10019

Cited by 11 publications

(6 citation statements)

References 37 publications

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“…At the time of release from the thymidine block, there is a relatively large population of cells with separated centrosomes, reflecting highly dynamic movement between parental centrioles throughout the cell cycle (36,37). The observed increase in separated centrosomes in nonirradiated cells (10-12 h) almost certainly reflects the physiological event of centrosome separation at the G 2 /M-phase transition (Fig.…”

Section: Centrosomal Separation Is Inhibited After Exposure To Dna-damentioning

confidence: 82%

Inhibition of Centrosome Separation after DNA Damage: A Role for Nek2

et al. 2004

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DNA damage results in cell cycle arrest in G2. Centrosomes also separate in G2, raising the question of whether separation occurs during the DNA damage-induced G2 arrest. Nek2, the mammalian homologue of NIMA, is a cell cycle-regulated serine/threonine protein kinase that regulates centrosome separation during G2. Here we show that damaged cells fail to activate Nek2. Both Nek2 levels and activity are reduced after DNA damage. Radiation inhibits the premature centrosome splitting induced by overexpression of Nek2, indicating that Nek2 is involved in activation of the G2 checkpoint and is not secondary to cell cycle arrest. We confirm using siRNA that centrosome separation and cell growth are impaired in the absence of Nek2. These studies define a previously unreported DNA damage response of inhibition of centrosome separation mechanistically linked to Nek2.

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Section: Centrosomal Separation Is Inhibited After Exposure To Dna-damentioning

confidence: 82%

Inhibition of Centrosome Separation after DNA Damage: A Role for Nek2

et al. 2004

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“…The simplest explanation for these observations is that dysregulated actin polymerization has a direct effect on cell growth and/or survival. The actin cytoskeleton plays a crucial role in mitosis, 28,29 and pharmacologically induced actin disorganization has been shown to activate a stress-activated mitogen-activated protein kinase pathway and lead to growth arrest. 30 Furthermore, cytokinesis requires the regulated formation of a contractile ring of actin and myosin that cleaves the cell in 2.…”

Section: Discussionmentioning

confidence: 99%

Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia

Ancliff

Blundell

Cory

et al. 2006

Blood

201

222

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“…The two centrioles of a centrosome are thought to carry distinct activities, with the larger mature "mother" centriole (MC) capturing and anchoring nucleated MTs and providing important signals to the midbody that promote cytokinesis [39,76,[94][95][96]. These functions are facilitated by the rotation and movement of the MC to the midbody prior to cytokinesis [76,94,96,97]. Inhibition of this process is associated with cytokinetic defects [96].…”

Section: Discussionmentioning

confidence: 99%

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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Post‐karyokinesis centrosome movement leaves a trail of unanswered questions

Cited by 11 publications

References 37 publications

Inhibition of Centrosome Separation after DNA Damage: A Role for Nek2

Inhibition of Centrosome Separation after DNA Damage: A Role for Nek2

Two novel activating mutations in the Wiskott-Aldrich syndrome protein result in congenital neutropenia

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

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