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Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
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Usp39 is essential for mitotic spindle checkpoint integrity and controls mRNA-levels of aurora B

Renske J van Leuken1, Mark P Luna-Vargas, Titia K Sixma

  • 1Department of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.

Cell Cycle (Georgetown, Tex.)
|August 30, 2008
PubMed

Insights

Usp39 is crucial for the mitotic spindle checkpoint and cell division. This protein regulates Aurora B mRNA splicing, not deubiquitinating activity, to ensure accurate chromosome segregation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Accurate chromosome segregation during mitosis depends on the spindle assembly checkpoint.
  • The Anaphase-promoting complex (APC/C) is a ubiquitin ligase regulated by this checkpoint.
  • Deubiquitinating enzymes (Dubs) play roles in regulating protein function and cellular processes.

Purpose of the Study:

  • To identify novel deubiquitinating enzymes involved in mitotic progression using a functional RNAi screen.
  • To investigate the role of Usp39 in maintaining the spindle checkpoint and ensuring successful cytokinesis.

Main Methods:

  • Functional RNA interference (RNAi)-based screening to identify Dubs.
  • Analysis of Usp39's enzymatic activity and its role in mRNA processing.
  • Assessment of Aurora B mRNA and protein levels upon Usp39 depletion.

Main Results:

  • Usp39 was identified as a novel factor essential for spindle checkpoint function and cytokinesis.
  • Usp39 lacks deubiquitinating activity despite possessing a ubiquitin-protease domain.
  • Depletion of Usp39 led to reduced Aurora B mRNA levels, suggesting a role in mRNA processing.
  • Exogenous expression of Aurora B cDNA did not rescue the checkpoint defect, but Aurora B expression was restored.

Conclusions:

  • Usp39 is critical for proper spindle checkpoint function and cytokinesis.
  • Usp39's role involves regulating the splicing of Aurora B mRNA and potentially other essential mRNAs.
  • This mechanism is vital for maintaining accurate chromosome segregation during cell division.

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