Antagonistic activities of CDC14B and CDK1 on USP9X regulate WT1-dependent mitotic transcription and survival.
A549 Cells
Apoptosis
CDC2 Protein Kinase
/ antagonists & inhibitors
Dual-Specificity Phosphatases
/ antagonists & inhibitors
Gene Knockdown Techniques
HEK293 Cells
HeLa Cells
Humans
Interleukin-8
/ metabolism
Mitosis
/ physiology
Phosphorylation
Transcription Factors
Ubiquitin Thiolesterase
/ drug effects
WT1 Proteins
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
09 03 2020
09 03 2020
Historique:
received:
18
04
2019
accepted:
17
02
2020
entrez:
11
3
2020
pubmed:
11
3
2020
medline:
3
7
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32152317
doi: 10.1038/s41467-020-15059-5
pii: 10.1038/s41467-020-15059-5
pmc: PMC7063047
doi:
Substances chimiques
CXCL8 protein, human
0
Interleukin-8
0
Transcription Factors
0
USP9X protein, human
0
WT1 Proteins
0
WT1 protein, human
0
CDC2 Protein Kinase
EC 2.7.11.22
CDK1 protein, human
EC 2.7.11.22
CDC14B protein, human
EC 3.1.3.48
Dual-Specificity Phosphatases
EC 3.1.3.48
Ubiquitin Thiolesterase
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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