Related Experiment Video

Updated: Dec 26, 2025

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

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

Michael Dietachmayr1,2, Abirami Rathakrishnan1,2, Oleksandra Karpiuk1,2

  • 1Department of Medicine III, Klinikum rechts der Isar, Technical University of Munich, 81675, Munich, Germany.

Nature Communications
|March 11, 2020
PubMed

Insights

The CDC14B phosphatase regulates mitotic survival by deubiquitylating USP9X, a key enzyme. This process stabilizes Wilms' tumor protein 1 (WT1), a mitotic transcription factor essential for cell survival during mitosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Mitotic regulation is crucial for cellular integrity, and its disruption is linked to cancer development and treatment resistance.
  • The Cdc14 phosphatase family plays a role in controlling mitosis, but the specific functions of its mammalian orthologue, CDC14B, are not well understood.

Purpose of the Study:

  • To elucidate the specific mitotic functions of the mammalian CDC14B orthologue.
  • To identify substrates and pathways regulated by CDC14B during mitosis.

Main Methods:

  • Proteome-wide screening to identify CDC14B-interacting proteins and substrates.
  • Phosphorylation site analysis (serine 2563) on USP9X.
  • Ubiquitination and stabilization assays for WT1.
  • Analysis of WT1's role as a mitotic transcription factor and its target genes.

Main Results:

  • CDC14B antagonizes CDK1-mediated phosphorylation of USP9X at serine 2563, which is essential for mitotic survival.
  • Phosphorylated USP9X deubiquitylates and stabilizes Wilms' tumor protein 1 (WT1).
  • WT1 acts as a mitotic transcription factor, regulating the expression of CXCL8/IL-8 to promote mitotic survival.

Conclusions:

  • A novel ubiquitin-dependent signaling pathway regulates mitotic survival.
  • This pathway involves CDC14B, USP9X, and WT1, directing a mitosis-specific transcription program.
  • Understanding this pathway offers potential insights into cancer biology and therapeutic strategies.

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