Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival

Michael Dietachmayr, Abirami Rathakrishnan, Oleksandra Karpiuk, Felix von Zweydorf, Thomas Engleitner, Vanesa Fernández-Sáiz, Petra Schenk, Marius Ueffing, Roland Rad, Martin Eilers, Christian Johannes Gloeckner, Katharina Clemm von Hohenberg () and Florian Bassermann ()
Additional contact information
Michael Dietachmayr: Technical University of Munich
Abirami Rathakrishnan: Technical University of Munich
Oleksandra Karpiuk: Technical University of Munich
Felix von Zweydorf: German Center for Neurodegenerative Diseases (DZNE)
Thomas Engleitner: Technical University of Munich
Vanesa Fernández-Sáiz: Technical University of Munich
Petra Schenk: Technical University of Munich
Marius Ueffing: University of Tübingen, Center for Ophthalmology, Institute for Ophthalmic Research
Roland Rad: Technical University of Munich
Martin Eilers: University of Würzburg
Christian Johannes Gloeckner: German Center for Neurodegenerative Diseases (DZNE)
Katharina Clemm von Hohenberg: Technical University of Munich
Florian Bassermann: Technical University of Munich

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-15059-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15059-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-15059-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().