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000144403 0247_ $$2doi$$a10.1038/s41418-019-0385-7
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000144403 0247_ $$2ISSN$$a1476-5403
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000144403 1001_ $$0P:(DE-He78)f08cb94a1ca44e0f65e828ea1c2edca4$$aRichter, Kai$$b0$$eFirst author
000144403 245__ $$aFBXO45-MYCBP2 regulates mitotic cell fate by targeting FBXW7 for degradation.
000144403 260__ $$aLondon$$bMacmillan$$c2020
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000144403 500__ $$a2020 Feb;27(2):758-772#EA:F045#LA:F045#
000144403 520__ $$aCell 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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000144403 7001_ $$0P:(DE-HGF)0$$aKschonsak, Yvonne T$$b1
000144403 7001_ $$0P:(DE-He78)df9c47af8df9bd3d1243d61712a864f5$$aVodicska, Barbara$$b2$$eLast author
000144403 7001_ $$0P:(DE-He78)b97fa0c782a162d952b6197f3b916379$$aHoffmann, Ingrid$$b3$$eLast author
000144403 773__ $$0PERI:(DE-600)1496681-5$$a10.1038/s41418-019-0385-7$$n2$$p758-772$$tCell death and differentiation$$v27$$x1476-5403$$y2020
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000144403 9141_ $$y2020
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