Microtubule Dynamics during the Cell Cycle: The Effects of Taxol and Nocodazole on the Microtubule System of Pt K2 Cells at Different Stages of the Mitotic Cycle

Brabander, M. De; Geuens, G.; Nuydens, Rony; Willebrords, R.; Aerts, F.; Mey, J. De; McIntosh, J. Richard

doi:10.1016/s0074-7696(08)60250-8

Cited by 136 publications

(89 citation statements)

References 72 publications

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“…length of the microtubule (De Brabander et al, 1986). On treatment with either drug, integral centrosomal proteins remain bound to centrosomal components, whereas microtubule-dependent centrosome-associated proteins are no longer retained at the MTOC (De Brabander et al, 1986). Under control conditions (untreated) SLMAP3M1 was found to colocalize with γ-tubulin (Fig.…”

Section: Slmap Is a Novel Component Of The Centrosomementioning

confidence: 92%

“…Lane 1 (lysed extract), lane 2 (crude centrosomes) and lanes 3-6 represent fractions obtained from sucrose density gradients. length of the microtubule (De Brabander et al, 1986). On treatment with either drug, integral centrosomal proteins remain bound to centrosomal components, whereas microtubule-dependent centrosome-associated proteins are no longer retained at the MTOC (De Brabander et al, 1986).…”

Section: Slmap Is a Novel Component Of The Centrosomementioning

confidence: 99%

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A novel isoform of sarcolemmal membrane-associated protein (SLMAP) is a component of the microtubule organizing centre

Guzzo

Sevinc

Salih

et al. 2004

Journal of Cell Science

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The microtubule organizing centre (MTOC) or the centrosome serves a crucial role in the establishment of cellular polarity, organization of interphase microtubules and the formation of the bipolar mitotic spindle. We have elucidated the genomic structure of a gene encoding the sarcolemmal membrane-associated protein (SLMAP), which encodes a 91 kDa polypeptide with a previously uncharacterized N-terminal sequence encompassing a forkhead-associated (FHA) domain that resides at the centrosome. Anti-peptide antibodies directed against SLMAP N-terminal sequences showed colocalization with γ-tubulin at the centrosomes at all phases of the cell cycle. Agents that specifically disrupt microtubules did not affect SLMAP association with centrosomes. Furthermore, SLMAP sequences directed a reporter green fluorescent protein (GFP) to the centrosome, and deletions of the newly identified N-terminal sequence from SLMAP prevented the centrosomal targeting. Deletion-mutant analysis concluded that overall, structural determinants in SLMAP were responsible for centrosomal targeting. Elevated levels of centrosomal SLMAP were found to be lethal, whereas mutants that lacked centrosomal targeting inhibited cell growth accompanied by an accumulation of cells at the G2/M phase of the cell cycle.

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Section: Slmap Is a Novel Component Of The Centrosomementioning

confidence: 92%

Section: Slmap Is a Novel Component Of The Centrosomementioning

confidence: 99%

A novel isoform of sarcolemmal membrane-associated protein (SLMAP) is a component of the microtubule organizing centre

Guzzo

Sevinc

Salih

et al. 2004

Journal of Cell Science

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“…Taxol appears to target microtubules specifically both in vitro and in vivo Horwitz, 1980, 1981;Manfredi et al, 1982;Manfredi and Horwitz, 1984;De Brabender et al, 1996). However, unlike classical antimicrotubule agents, such as colchicine and vinblastine, that induce microtubule disassembly and paracrystal formation (Wilson et al, 1974), the antitumour activity of taxol has been demonstrated to be associated with microtubule stabilisation (Manfredi and Horwitz, 1984;Horwitz et al, 1986) and with the arrest of cells in the G2/M phase of the cell cycle Slichenmyer and von Hoff, 1991;Rowinsky et al, 1992).…”

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confidence: 99%

Delayed expression of apoptosis in human lymphoma cells undergoing low-dose taxol-induced mitotic stress

2003

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The links between low-dose range taxol-induced mitotic arrest and the subsequent engagement of apoptosis are important for identifying the routes to therapeutic action. Here we have investigated the timing of cell-cycle perturbation and cell death responses following continuous exposure to clinically relevant drug concentrations (1 -20 nM). Following 8 h of exposure to taxol, the cell line DoHH2 (p53 wild type) exhibited mitotic arrest and engagement of apoptosis, whereas the cell line SU-DHL-4 (p53 mutant) breached cell-cycle arrest with progression to an abnormal cycle and a 24 h delay in the engagement of apoptosis. Imaging showed equivalent dysfunction of mitotic spindles in both cell lines. The results of kinetic analyses indicated that although cell death may occur at different stages of progression through mitosis and subsequent cell cycles, the overall kinetics of cell death relate to the rate of arrival at a critical event window in the cell cycle. We propose a simple model of low-dose taxol-induced cell death for cycling populations in which mitotic stress acts as a primary trigger for apoptosis with equivalent but potentially delayed outcomes. This view provides a rationale for the clinical effectiveness of this agent, independent of the initial capacity of the tumour cell to engage apoptosis due, for example, to mutant p53 expression. The results provide a perspective for the design of combination regimens that include low-dose taxol and a component that may disturb mitotic delivery.

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“…Vincristine induces the formation of paracrystalline aggregates of tubulin, which leads to microtubule depolymerization. Paclitaxel binds tightly to polymers and inhibits microtubule depolymerization [12,20,35].…”

Section: Antimicrotubule Drugsmentioning

confidence: 99%

A Novel Strategy for Growth Suppression of Glioma Cells: Targeting Microtubules

Matsuno

Nagashima

2004

Acta Histochem. Cytochem

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Paclitaxel, one of the antimicrotubule drugs, can suppress the growth of C6 glioma cells. However, paclitaxel may also accelerate in vitro locomotion of glioma cells. Another choice of antimicrotubule drugs is estramustine which has cytotoxic effects in human and rat glioma cells. We verified the role of microtubule-associated protein (MAP) 1A in proliferation of rat C6 glioma cells. We confirmed that the in vitro and in vivo suppression of MAP 1A using antisense synthetic phosphorothioate oligonucleotide can inhibit the proliferation of rat C6 glioma cells and may thus serve as a novel antisense therapy for glioma. It is noteworthy that the therapies targeting microtubules and MAPs, especially those using antisense strategy, are useful antitumor therapies for gliomas.

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Microtubule Dynamics during the Cell Cycle: The Effects of Taxol and Nocodazole on the Microtubule System of Pt K2 Cells at Different Stages of the Mitotic Cycle

Cited by 136 publications

References 72 publications

A novel isoform of sarcolemmal membrane-associated protein (SLMAP) is a component of the microtubule organizing centre

A novel isoform of sarcolemmal membrane-associated protein (SLMAP) is a component of the microtubule organizing centre

Delayed expression of apoptosis in human lymphoma cells undergoing low-dose taxol-induced mitotic stress

A Novel Strategy for Growth Suppression of Glioma Cells: Targeting Microtubules

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