Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus.

Jackman, Mark; Firth, M.; Pines, Jonathon

doi:10.1002/j.1460-2075.1995.tb07153.x

Cited by 248 publications

(190 citation statements)

References 51 publications

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“…However, it is also apparent that both cell lines exhibit increased cyclin B1 expression at doses of taxol that did not induce a measurable G2/M arrest on the basis of single parameter DNA measurements. Cyclin B1 is known to be associated with microtubules (Jackman et al, 1995) and our observations suggest that taxol-induced tubulin polymerisation, at concentrations insufficient to induce a cell-cycle arrest, can stabilise cyclin B1 levels. …”

Section: Taxol Induces a Sustained Cell-cycle Arrest In Dohh2 Cells Amentioning

confidence: 52%

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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Section: Taxol Induces a Sustained Cell-cycle Arrest In Dohh2 Cells Amentioning

confidence: 52%

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

2003

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“…Reexamination of published images shows association of CyclinB with the nuclear envelope at the onset of mitosis in Drosophila embryos (Wakefield et al, 2000, supplementary material) and subpopulations of Cyclin B1 and Cdc2 localized as a perinuclear ring during interphase in HeLa cells (Bailly et al, 1992;Pockwinse et al, 1997;Clute and Pines, 1999). These patterns may have been overlooked because of the strong localization of Cyclin B1 to centrosomes throughout interphase (Bailly et al, 1992;Jackman et al, 1995) or microtubules at mitosis (Jackman et al, 1995) and that of Cyclin B2 at the Golgi in the pericentriolar area (Jackman et al, 1995;reviewed in Beckhelling et al, 2000;Ohi and Gould, 1999;Pines, 1999). Furthermore, recent detailed observations of Cyclin B distribution by immunofluorescence and Cyclin B-GFP expression in prophase starfish oocytes has revealed a clear association with the nuclear envelope (Terasaki, personal communication).…”

Section: Discussionmentioning

confidence: 99%

“…A number of localization studies concerning MPF and its regulators performed in a variety of cell types are consistent with this possibility. B Cyclins, Cdc25, Polo kinase, Wee1, and Myt1 have all been found to localize to structures such as prophase microtubule asters, centrosomes, nuclei, endoplasmic reticulum (ER), and Golgi, their associations with these structures varying with cell cycle time and activity of the molecules involved (Bailly et al, 1989(Bailly et al, , 1992Jackman et al, 1995;Liu et al, 1997;Sakamoto et al, 1998;Ashcroft et al, 1999;Ohi and Gould, 1999;Pines, 1999;Charrasse et al, 2000;Takizawa and Morgan, 2000). Very little is known about the subcellular localization of MPF and its regulators in amphibian eggs.…”

Section: Introductionmentioning

confidence: 99%

Pre-M Phase-promoting Factor Associates with Annulate Lamellae inXenopusOocytes and Egg Extracts

Beckhelling

Chang

Chevalier

et al. 2003

MBoC

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We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates. INTRODUCTIONThe structural changes accompanying mitosis and meiosis are governed in almost all species by M phase-promoting factor (MPF) (Masui and Markert, 1971), a complex of Cyclin B and the kinase Cdc2 (reviewed in Nigg, 1995;Morgan, 1997). Direct and indirect targets for MPF include the nuclear envelope and lamina, chromatin proteins, and regulators of mitotic spindle formation (Moreno and Nurse, 1990;Norbury and Nurse, 1992). MPF activation requires the continuous synthesis and accumulation during interphase of Cyclin B, which binds Cdc2 to form inactive pre-MPF. Pre-MPF is maintained inactive by inhibitory phosphorylation on Cdc2 by the Wee1 and Myt1 kinases. At the onset of mitosis, rapid MPF activation is favored by a positive feedback loop involving Cdc25 phosphatases, MPF itself, and Polo-like kinases. Degradation of Cyclin B at the metaphaseto-anaphase transition by the anaphase promoting complex (APC) destroys the MPF complex and causes exit from mitosis (reviewed in Nurse, 1990; Whitaker and Patel., 1990;Norbury and Nurse, 1992;Nigg, 1995;Morgan, 1997Morgan, , 1999Beckhelling and Ford, 1998;O'Farrell, 2001).Amphibian eggs have proved extremely useful for the study of MPF regulation. Cycles of Cyclin B accumulation and destruction sufficient to drive synchronous cell cycles in the absence of any other protein synthesis occur in both fertilized or activated eggs and in egg extracts (Murray and Kirschner, 1989;Hartley et al., 1996). Although MPF activation cycles in amphibian oocytes and eggs can continue in the absence of nuclei and microtubules (Hara et al., 1980;Shinagawa, 1983;Gerhart et al., 1984;Newport and Kirschner, 1984;Kimelman et al., 1987;Shinagawa, 1992) both in manipulate...

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“…Cyclin B1 is essentially cytoplasmic, partially colocalizes with microtubules during interphase, and abruptly translocates into the nucleus upon mitosis entry (Jackman et al, 1995;Hagting et al, 1999), a process that is delayed in cyclin A2-depleted cells (Gong et al, 2007). Human cyclin B2 colocalizes with the Golgi apparatus and contributes to its fragmentation during mitosis (Jackman et al, 1995;Draviam et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2

2007

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Cyclin-dependent kinase 1 (CDK1) plays a crucial role in establishing metaphase and has also been shown to prevent DNA re-replication. Cyclins B1 and B2 are two known activators of CDK1 operating during mitosis in human cells. Little is known about the specific roles of each of these cyclins in CDK1 activation, but cyclin B2 is thought to play a minor role and to be unable to replace cyclin B1 for mitosis completion. In our study, we found that severe reduction by separate RNA interference of either cyclin B1 or cyclin B2 protein levels results in little or no alteration of the cell cycle and, more specifically, of mitosis progression. In contrast, simultaneous depletion of both B-type cyclins leads to massive accumulation of 4N cells, mitotic failure, premature mitosis exit and DNA rereplication. These defects can be corrected by the ectopic expression of a cyclin B2 resistant to the short hairpin RNA. Altogether, these data show that, in cycling human cells, cyclin B2 can compensate for the downregulation of cyclin B1 during mitosis. They also clearly implicate cyclins B1 and B2 as crucial activators of CDK1 in its biological function of DNA re-replication prevention.

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Human cyclins B1 and B2 are localized to strikingly different structures: B1 to microtubules, B2 primarily to the Golgi apparatus.

Cited by 248 publications

References 51 publications

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

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

Pre-M Phase-promoting Factor Associates with Annulate Lamellae inXenopusOocytes and Egg Extracts

Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2

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