001     144403
005     20240229123018.0
024 7 _ |a 10.1038/s41418-019-0385-7
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024 7 _ |a 1350-9047
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024 7 _ |a 1476-5403
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037 _ _ |a DKFZ-2019-01856
041 _ _ |a eng
082 _ _ |a 610
100 1 _ |a Richter, Kai
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245 _ _ |a FBXO45-MYCBP2 regulates mitotic cell fate by targeting FBXW7 for degradation.
260 _ _ |a London
|c 2020
|b Macmillan
336 7 _ |a article
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500 _ _ |a 2020 Feb;27(2):758-772#EA:F045#LA:F045#
520 _ _ |a Cell fate decision upon prolonged mitotic arrest induced by microtubule-targeting agents depends on the activity of the tumor suppressor and F-box protein FBXW7. FBXW7 promotes mitotic cell death and prevents premature escape from mitosis through mitotic slippage. Mitotic slippage is a process that can cause chemoresistance and tumor relapse. Therefore, understanding the mechanisms that regulate the balance between mitotic cell death and mitotic slippage is an important task. Here we report that FBXW7 protein levels markedly decline during extended mitotic arrest. FBXO45 binds to a conserved acidic N-terminal motif of FBXW7 specifically under a prolonged delay in mitosis, leading to ubiquitylation and subsequent proteasomal degradation of FBXW7 by the FBXO45-MYCBP2 E3 ubiquitin ligase. Moreover, we find that FBXO45-MYCBP2 counteracts FBXW7 in that it promotes mitotic slippage and prevents cell death in mitosis. Targeting this interaction represents a promising strategy to prevent chemotherapy resistance.
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700 1 _ |a Kschonsak, Yvonne T
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700 1 _ |a Vodicska, Barbara
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700 1 _ |a Hoffmann, Ingrid
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773 _ _ |a 10.1038/s41418-019-0385-7
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|t Cell death and differentiation
|v 27
|y 2020
|x 1476-5403
909 C O |p VDB
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910 1 _ |a Deutsches Krebsforschungszentrum
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|v Infections and cancer
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914 1 _ |y 2020
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