Journal Article

DZNE-2020-01409

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival.

Dietachmayr, M. ; Rathakrishnan, A. ; Karpiuk, O. ; von Zweydorf, F.DZNE* ; Engleitner, T. ; Fernández-Sáiz, V. ; Schenk, P. ; Ueffing, M. ; Rad, R. ; Eilers, M. ; Gloeckner, C. J.DZNE* ; Clemm von Hohenberg, K. (Corresponding author) ; Bassermann, F.

2020
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-020-15059-5

Abstract: 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.

Keyword(s): A549 Cells (MeSH) ; Apoptosis (MeSH) ; CDC2 Protein Kinase: antagonists & inhibitors (MeSH) ; Dual-Specificity Phosphatases: antagonists & inhibitors (MeSH) ; Gene Knockdown Techniques (MeSH) ; HEK293 Cells (MeSH) ; HeLa Cells (MeSH) ; Humans (MeSH) ; Interleukin-8: metabolism (MeSH) ; Mitosis: physiology (MeSH) ; Phosphorylation (MeSH) ; Transcription Factors (MeSH) ; Ubiquitin Thiolesterase: drug effects (MeSH) ; Ubiquitin Thiolesterase: genetics (MeSH) ; Ubiquitin Thiolesterase: metabolism (MeSH) ; WT1 Proteins: genetics (MeSH) ; WT1 Proteins: metabolism (MeSH) ; CXCL8 protein, human ; Interleukin-8 ; Transcription Factors ; USP9X protein, human ; WT1 Proteins ; WT1 protein, human ; CDC2 Protein Kinase ; CDK1 protein, human ; CDC14B protein, human ; Dual-Specificity Phosphatases ; Ubiquitin Thiolesterase

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Contributing Institute(s):

1. Functional Neuroproteomics and Translational Biomarkers in Neurodegenerative Diseases (AG Gloeckner)

Research Program(s):

1. 345 - Population Studies and Genetics (POF3-345) (POF3-345)

Appears in the scientific report 2020

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Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Gloeckner, C. J. (Last author)DZNE*
Dataset: Identification of mitotic substrates of phospho-regulated USP9X
PRoteomics IDEntifications Database (2020)2020   Fulltext BibTeX | EndNote: XML, Text | RIS

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Gloeckner, C. J. (Last author)DZNE*
Dataset: USP9X phosphopeptide mapping
PRoteomics IDEntifications Database (2020)2020   Fulltext BibTeX | EndNote: XML, Text | RIS

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