TRIP13 Regulates Both the Activation and Inactivation of the Spindle-Assembly Checkpoint

Hoi Tang Ma1, Randy Yat Choi Poon1

  • 1Division of Life Science, Center for Cancer Research and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.

Cell Reports
|February 3, 2016
PubMed

Insights

The spindle-assembly checkpoint relies on MAD2 inactivation, a process involving p31(comet) and TRIP13. TRIP13 is essential for this inactivation, while p31(comet) enhances it, revealing their roles in cell cycle regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Biochemical studies identified p31(comet) and TRIP13 as crucial for MAD2 inactivation.
  • Understanding the cellular roles of p31(comet) and TRIP13 in mitosis and checkpoint regulation is essential.

Purpose of the Study:

  • To determine if p31(comet) and TRIP13 are required for mitotic exit at the cellular level.
  • To elucidate the specific roles of p31(comet) and TRIP13 in MAD2 inactivation and spindle-assembly checkpoint function.

Main Methods:

  • Gene ablation of p31(comet) and TRIP13 individually and together in human cells.
  • Analysis of mitotic progression, MAD2 inactivation status, and spindle-assembly checkpoint activation in gene-deficient cells.

Main Results:

  • Neither p31(comet) nor TRIP13 ablation completely blocked mitosis.
  • MAD2 inactivation was partially impaired in p31(comet)-deficient cells, but completely blocked in TRIP13-deficient cells.
  • TRIP13-deficient cells failed to activate the spindle-assembly checkpoint, despite MAD2 inactivation defects.

Conclusions:

  • TRIP13 is essential for MAD2 inactivation and spindle-assembly checkpoint activation.
  • p31(comet) enhances TRIP13-mediated MAD2 inactivation but is not strictly required.
  • These findings establish a new paradigm for the roles of p31(comet) and TRIP13 in both checkpoint activation and inactivation during mitosis.

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