Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31(comet)

Esther Eytan1, Kexi Wang2, Shirly Miniowitz-Shemtov1

  • 1Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;

Insights

The mitotic checkpoint ensures correct chromosome attachment. Researchers identified Thyroid Receptor Interacting Protein 13 (TRIP13) as a key factor, along with p31(comet), in disassembling the Mitotic Checkpoint Complex (MCC) to inactivate the checkpoint.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The spindle assembly checkpoint (SAC) prevents premature anaphase onset by inhibiting the Anaphase-Promoting Complex/Cyclosome (APC/C).
  • Mitotic Checkpoint Complex (MCC) assembly is crucial for SAC activity, but its disassembly mechanism remains unclear.
  • Previous work indicated ATP hydrolysis is necessary for p31(comet)-mediated MCC disassembly.

Purpose of the Study:

  • To identify factors involved in MCC disassembly.
  • To elucidate the role of Thyroid Receptor Interacting Protein 13 (TRIP13) in MCC disassembly and SAC inactivation.

Main Methods:

  • Utilized HeLa cell extracts.
  • Investigated ATP- and p31(comet)-dependent disassembly of Cdc20-Mad2 subcomplex.
  • Assessed the effect of TRIP13 and p31(comet) on MCC disassembly and APC/C inhibition.

Main Results:

  • Identified TRIP13, an AAA-ATPase, as a factor promoting p31(comet)-dependent disassembly of a Cdc20-Mad2 subcomplex.
  • Demonstrated that TRIP13 and p31(comet) cooperate to release Mad2 from MCC.
  • Showed that TRIP13 and p31(comet) facilitate complete MCC disassembly and abrogate APC/C inhibition.

Conclusions:

  • TRIP13 plays a central role in MCC disassembly.
  • TRIP13 and p31(comet) are key components in the pathway for spindle assembly checkpoint inactivation.
  • Understanding these mechanisms is critical for comprehending cell cycle regulation.

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