TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC

Nat Commun. 2018 Oct 19;9(1):4354. doi: 10.1038/s41467-018-06774-1.


The mitotic checkpoint ensures accurate chromosome segregation through assembly of the mitotic checkpoint complex (MCC), a soluble inhibitor of the anaphase-promoting complex/cyclosome (APC/C) produced by unattached kinetochores. MCC is also assembled during interphase by Mad1/Mad2 bound at nuclear pores, thereby preventing premature mitotic exit prior to kinetochore maturation and checkpoint activation. Using degron tagging to rapidly deplete the AAA+ ATPase TRIP13, we show that its catalytic activity is required to maintain a pool of open-state Mad2 for MCC assembly, thereby supporting mitotic checkpoint activation, but is also required for timely mitotic exit through catalytic disassembly of MCC. Strikingly, combining TRIP13 depletion with elimination of APC15-dependent Cdc20 ubiquitination/degradation results in a complete inability to exit mitosis, even when MCC assembly at unattached kinetochores is prevented. Thus, mitotic exit requires MCC produced either in interphase or mitosis to be disassembled by TRIP13-catalyzed removal of Mad2 or APC15-driven ubiquitination/degradation of its Cdc20 subunit.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • ATPases Associated with Diverse Cellular Activities / physiology*
  • Anaphase-Promoting Complex-Cyclosome / genetics
  • Anaphase-Promoting Complex-Cyclosome / metabolism
  • Anaphase-Promoting Complex-Cyclosome / physiology*
  • Cdc20 Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Interphase
  • Kinetochores / physiology*
  • M Phase Cell Cycle Checkpoints*
  • Mad2 Proteins / metabolism
  • Mitosis / physiology*


  • ANAPC15 protein, human
  • Cdc20 Proteins
  • Cell Cycle Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • CDC20 protein, human
  • Anaphase-Promoting Complex-Cyclosome
  • ATPases Associated with Diverse Cellular Activities
  • TRIP13 protein, human