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• W2466563707 abstract "Inhibition of the microtubule (MT) motor protein Eg5 results in a mitotic arrest due to the formation of monopolar spindles, making Eg5 an attractive target for anti-cancer therapies. However, Eg5-independent pathways for bipolar spindle formation exist, which might promote resistance to treatment with Eg5 inhibitors. To identify essential components for Eg5-independent bipolar spindle formation, we performed a genome-wide siRNA screen in Eg5-independent cells (EICs). We find that the kinase Aurora A and two kinesins, MCAK and Kif18b, are essential for bipolar spindle assembly in EICs and in cells with reduced Eg5 activity. Aurora A promotes bipolar spindle assembly by phosphorylating Kif15, hereby promoting Kif15 localization to the spindle. In turn, MCAK and Kif18b promote bipolar spindle assembly by destabilizing the astral MTs. One attractive way to interpret our data is that, in the absence of MCAK and Kif18b, excessive astral MTs generate inward pushing forces on centrosomes at the cortex that inhibit centrosome separation. Together, these data suggest a novel function for astral MTs in force generation on spindle poles and how proteins involved in regulating microtubule length can contribute to bipolar spindle assembly." @default.
• W2466563707 created "2016-07-22" @default.
• W2466563707 creator A5021651693 @default.
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• W2466563707 date "2016-06-29" @default.
• W2466563707 modified "2023-10-10" @default.
• W2466563707 title "Aurora A, MCAK, and Kif18b promote Eg5-independent spindle formation" @default.
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• W2466563707 doi "https://doi.org/10.1007/s00412-016-0607-4" @default.
• W2466563707 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5509784" @default.
• W2466563707 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27354041" @default.
• W2466563707 hasPublicationYear "2016" @default.
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