Aurora-A and hBora Join the Game of Polo

Macůrek, Libor; Lindqvist, Arne; Medema, René H.

doi:10.1158/0008-5472.can-09-0142

Cited by 44 publications

(37 citation statements)

References 33 publications

(63 reference statements)

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“…42 Most interestingly, different studies have shown a certain overlap between Aurora kinases and PLK1 coregulating several processes in mitosis, and the inhibition of either of them has been shown to cause similar phenotypes. 43 In conclusion, PLK1 inhibition causes a decrease in proliferation and clonogenic formation, and an increase in apoptosis and sensitization to radiation. These results indicate the importance of PLK1 in GBM carcinogenesis, implying the possibility of using this kinase as a potential target to radiosensitize high-grade gliomas and to improve the actual treatment.…”

Section: Pezuk Et Almentioning

confidence: 88%

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk

Brassesco

Morales

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. For cell cycle analysis, T98G, U251, U343 MG-a, LN319, SF188, U138 MG, and U87 MG cell lines were treated with 10, 50, or 100 nM of BI 2536 for 24 hours. In addition, cell cultures exposed to BI 2536 50 nM for 24 hours were irradiated with c-rays from 60 Cobalt source at final doses of 2, 4, and 6 Gy. Combinatorial effects were evaluated through proliferation and clonogenic capacity assays. Treatment with BI 2536 caused mitotic arrest after 24 hours, and increased apoptosis in GBM cells. Moreover, our results demonstrate that pretreatment with this drug sensitized six out of seven GBM cell lines to different doses of c-irradiation as shown by decreased growth and abrogation of colony-formation capacity. Our data suggest that PLK1 blockage has a radiosensitizing effect on GBM, which could improve treatment strategies for this devastating tumor.

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Section: Pezuk Et Almentioning

confidence: 88%

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk

Brassesco

Morales

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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“…However, Plk1 is also active in mitosis despite the fact that hBora is degraded (Chan et al, 2008;Seki et al, 2008a). This indicates that either Aurora A uses another cofactor to activate Plk1 or that another kinase is required for Plk1 activation during mitosis progression (Macurek et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle progression

2010

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During asymmetric cell division, cell polarity and cell cycle progression are tightly coordinated, yet mechanisms controlling both these events are poorly understood. Here we show that the Bora homologue SPAT-1 regulates both PAR polarity and cell cycle progression in C. elegans embryos. We find that, similarly to mammalian cells, SPAT-1 acts with PLK-1 and not with the mitotic kinase Aurora A (AIR-1), as shown in Drosophila. SPAT-1 binds to PLK-1, and depletion of SPAT-1 or PLK-1 leads to similar cell division defects in early embryos, which differ from the defects caused by depletion of AIR-1. Additionally, SPAT-1 and PLK-1 depletion causes impaired polarity with abnormal length of the anterior and posterior PAR domains, and partial plk-1(RNAi) or spat-1(RNAi), but not air-1(RNAi), can rescue the lethality of a par-2 mutant. SPAT-1 is enriched in posterior cells, and this enrichment depends on PAR polarity and PLK-1. Taken together, our data suggest a model in which SPAT-1 promotes the activity of PLK-1 to regulate both cell polarity and cell cycle timing during asymmetric cell division, providing a link between these two processes

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“…For more detailed information on Aurora kinases, the reader is referred to several excellent reviews. [23][24][25][26]37,38,42 Two Distinct Cofactors, Cep192 and TPX2, Control Aurora A Localization and Activity at Centrosomes and Spindle…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

“…14,28,29,31,32 However, TPX2 is not involved in AurA recruitment various aspects of mitosis and cytokinesis in a cooperative manner. [22][23][24][25][26] Aurora A and Aurora B Regulation:…”

Section: Microtubules Respectivelymentioning

confidence: 99%

Aurora kinases and spindle assembly: Variations on a common theme?

Joukov

2011

Cell Cycle

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Aurora-A and hBora Join the Game of Polo

Cited by 44 publications

References 33 publications

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

SPAT-1/Bora acts with Polo-like kinase 1 to regulate PAR polarity and cell cycle progression

Aurora kinases and spindle assembly: Variations on a common theme?

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