Home > Publications Database > Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival. > print

001     153412
005     20240321221044.0
024 7 _ |a 10.1038/s41467-020-15059-5
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037 _ _ |a DZNE-2020-01409
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Dietachmayr, Michael
|b 0
245 _ _ |a Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival.
260 _ _ |a [London]
|c 2020
|b Nature Publishing Group UK
336 7 _ |a article
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520 _ _ |a Regulation of mitosis secures cellular integrity and its failure critically contributes to the development, maintenance, and treatment resistance of cancer. In yeast, the dual phosphatase Cdc14 controls mitotic progression by antagonizing Cdk1-mediated protein phosphorylation. By contrast, specific mitotic functions of the mammalian Cdc14 orthologue CDC14B have remained largely elusive. Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. We further demonstrate that WT1 functions as a mitotic transcription factor and specify CXCL8/IL-8 as a target gene of WT1 that conveys mitotic survival. Together, we describe a ubiquitin-dependent signaling pathway that directs a mitosis-specific transcription program to regulate mitotic survival.
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650 _ 7 |a CXCL8 protein, human
|2 NLM Chemicals
650 _ 7 |a Interleukin-8
|2 NLM Chemicals
650 _ 7 |a Transcription Factors
|2 NLM Chemicals
650 _ 7 |a USP9X protein, human
|2 NLM Chemicals
650 _ 7 |a WT1 Proteins
|2 NLM Chemicals
650 _ 7 |a WT1 protein, human
|2 NLM Chemicals
650 _ 7 |a CDC2 Protein Kinase
|0 EC 2.7.11.22
|2 NLM Chemicals
650 _ 7 |a CDK1 protein, human
|0 EC 2.7.11.22
|2 NLM Chemicals
650 _ 7 |a CDC14B protein, human
|0 EC 3.1.3.48
|2 NLM Chemicals
650 _ 7 |a Dual-Specificity Phosphatases
|0 EC 3.1.3.48
|2 NLM Chemicals
650 _ 7 |a Ubiquitin Thiolesterase
|0 EC 3.4.19.12
|2 NLM Chemicals
650 _ 2 |a A549 Cells
|2 MeSH
650 _ 2 |a Apoptosis
|2 MeSH
650 _ 2 |a CDC2 Protein Kinase: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Dual-Specificity Phosphatases: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Gene Knockdown Techniques
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Interleukin-8: metabolism
|2 MeSH
650 _ 2 |a Mitosis: physiology
|2 MeSH
650 _ 2 |a Phosphorylation
|2 MeSH
650 _ 2 |a Transcription Factors
|2 MeSH
650 _ 2 |a Ubiquitin Thiolesterase: drug effects
|2 MeSH
650 _ 2 |a Ubiquitin Thiolesterase: genetics
|2 MeSH
650 _ 2 |a Ubiquitin Thiolesterase: metabolism
|2 MeSH
650 _ 2 |a WT1 Proteins: genetics
|2 MeSH
650 _ 2 |a WT1 Proteins: metabolism
|2 MeSH
700 1 _ |a Rathakrishnan, Abirami
|b 1
700 1 _ |a Karpiuk, Oleksandra
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700 1 _ |a von Zweydorf, Felix
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700 1 _ |a Engleitner, Thomas
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700 1 _ |a Fernández-Sáiz, Vanesa
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700 1 _ |a Schenk, Petra
|b 6
700 1 _ |a Ueffing, Marius
|b 7
700 1 _ |a Rad, Roland
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700 1 _ |a Eilers, Martin
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700 1 _ |a Gloeckner, Christian Johannes
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700 1 _ |a Clemm von Hohenberg, Katharina
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700 1 _ |a Bassermann, Florian
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773 _ _ |a 10.1038/s41467-020-15059-5
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