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Updated: Oct 13, 2025

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
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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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Mitotic phosphorylation of tumor suppressor DAB2IP maintains spindle assembly checkpoint and chromosomal stability

Lan Yu1,2, Yue Lang3, Ching-Cheng Hsu1

  • 1Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Oncogene
|November 14, 2021
PubMed

Insights

DAB2IP phosphorylation by Cdks regulates the spindle assembly checkpoint (SAC) in prostate cancer. Loss of this phosphorylation impairs SAC, increasing chromosomal instability (CIN) and promoting tumor growth.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Chromosomal instability (CIN) drives cancer development, often due to spindle assembly checkpoint (SAC) dysregulation.
  • DAB2IP, frequently silenced in advanced prostate cancer (PCa), is linked to aggressive phenotypes and mitotic regulation.
  • Previous work established DAB2IP's role in activating PLK1 for mitotic control.

Purpose of the Study:

  • To elucidate the novel role of DAB2IP phosphorylation in SAC regulation.
  • To investigate the mechanism by which DAB2IP interacts with PLK1 and Cdc20.
  • To determine the consequences of impaired DAB2IP phosphorylation on CIN and tumorigenesis.

Main Methods:

  • Investigated DAB2IP phosphorylation by Cyclin-dependent kinases (Cdks).
  • Assessed the impact of phosphorylation on DAB2IP's interaction with PLK1 and Cdc20.
  • Analyzed the effect of altered DAB2IP phosphorylation on the anaphase-promoting complex/cyclosome (APC/C) and SAC function.
  • Utilized depletion studies to evaluate the role of DAB2IP phosphorylation in chromosome missegregation and CIN.

Main Results:

  • Discovered that Cdks phosphorylate DAB2IP during mitosis, mediating its interaction with PLK1 and activating the PLK1-Mps1 pathway.
  • Demonstrated that phosphorylated DAB2IP inhibits Cdc20 ubiquitylation, preventing premature APC/C-MCC release and stabilizing the SAC.
  • Showed that loss of Cdk-mediated DAB2IP phosphorylation destabilizes the mitotic checkpoint complex (MCC), impairs the SAC, and increases chromosome missegregation and CIN.

Conclusions:

  • DAB2IP acts as a scaffold, facilitating PLK1-Mps1 interaction with Cdc20 for SAC integrity.
  • Impaired DAB2IP phosphorylation leads to SAC dysfunction, promoting CIN and contributing to aggressive PCa.
  • Targeting the SAC in DAB2IP-deficient aggressive PCa, which has a weak SAC, offers a potential therapeutic strategy.

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