Aneuploid colon cancer cells have a robust spindle checkpoint

Tighe, Anthony; Johnson, Victoria L.; Albertella, Mark R.; Taylor, Stephen S.

doi:10.1093/embo-reports/kve127

Cited by 154 publications

(121 citation statements)

References 34 publications

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“…It is conceivable that direct dephosphorylation via PP2A could play an important role. Some of the plus end-binding MAPs, such as EB1 and APC, have also been clearly localized to centrosomes [72,89,90], and ectopic expression of either induces microtubule bundling and nocodazole resistant microtubles. Interestingly, APC associates with PP2A B' subunits [91], though the importance of this association for its cytoskeletal functions is unknown.…”

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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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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“…Despite the fact that nearly 70% of all cancers demonstrate aneuploidy (including both ATL and HTLV-I infected cells), only rarely have genetic defects been identified in mitotic checkpoint genes, implying that other events must alter MSC function (Shimoyama, 1991;Cahill et al, 1998;Tighe et al, 2001). The MSC, responsible for regulating the onset of anaphase and the cell's subsequent commitment to divide, is regulated by at least seven known proteins including: MAD1, -2, -3 (Li and Murray, 1991); BUB (budding uninhibited by benzimidazole) -1, -2, -3 (Hoyt et al, 1991); and MPS1 (monopolar spindle 1) (Abrieu et al, 2001).…”

Section: Effects Of Tax On Chromosome Segregation and Aneuploidymentioning

confidence: 99%

Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response

2005

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“…Despite the fact that nearly 70% of all cancers demonstrate aneuploidy (including both ATLand HTLV-I-infected cells), only rarely have genetic defects been identified in mitotic checkpoint genes, implying that other events must alter function of the mitotic spindle checkpoint (MSC) (Shimoyama, 1991;Cahill et al, 1998;Tighe et al, 2001). The MSC, responsible for regulating the onset of anaphase and the cell's subsequent commitment to divide, is regulated by at least seven known proteins including: mitotic arrest-defective (MAD) -1, -2, -3 (Li and Murray, 1991); budding uninhibited by benzimidazole (BUB) -1, -2, -3 (Hoyt et al, 1991); and monopolar spindle 1 (MPS1) (Godden-Kent et al, 1997;Abrieu et al, 2001).…”

Section: Effects Of Tax On Aneuploidymentioning

confidence: 99%

Cellular Transformation by the HTLV-I Tax Protein, a Jack-of-All-Trades

2003

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Aneuploid colon cancer cells have a robust spindle checkpoint

Abstract: Colon cancer cells frequently display minisatellite instability (MIN) or chromosome instability (CIN). While MIN is caused

Cited by 154 publications

References 34 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

Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response

Cellular Transformation by the HTLV-I Tax Protein, a Jack-of-All-Trades

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