Role of CCT chaperonin in the disassembly of mitotic checkpoint complexes

Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):956-961. doi: 10.1073/pnas.1620451114. Epub 2017 Jan 17.


The mitotic checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. When this checkpoint is active, a mitotic checkpoint complex (MCC), composed of the checkpoint proteins Mad2, BubR1, Bub3, and Cdc20, is assembled. MCC inhibits the ubiquitin ligase anaphase promoting complex/cyclosome (APC/C), whose action is necessary for anaphase initiation. When the checkpoint signal is turned off, MCC is disassembled, a process required for exit from checkpoint-arrested state. Different moieties of MCC are disassembled by different ATP-requiring processes. Previous work showed that Mad2 is released from MCC by the joint action of the TRIP13 AAA-ATPase and the Mad2-binding protein p31comet Now we have isolated from extracts of HeLa cells an ATP-dependent factor that releases Cdc20 from MCC and identified it as chaperonin containing TCP1 or TCP1-Ring complex (CCT/TRiC chaperonin), a complex known to function in protein folding. Bacterially expressed CCT5 chaperonin subunits, which form biologically active homooligomers [Sergeeva, et al. (2013) J Biol Chem 288(24):17734-17744], also promote the disassembly of MCC. CCT chaperonin further binds and disassembles subcomplexes of MCC that lack Mad2. Thus, the combined action of CCT chaperonin with that of TRIP13 ATPase promotes the complete disassembly of MCC, necessary for the inactivation of the mitotic checkpoint.

Keywords: cell cycle; protein degradation; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / physiology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Cdc20 Proteins / metabolism
  • Cell Cycle Proteins / physiology
  • Chaperonin Containing TCP-1 / physiology*
  • HeLa Cells
  • Humans
  • M Phase Cell Cycle Checkpoints / physiology*
  • Mad2 Proteins / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Recombinant Proteins / metabolism
  • Sf9 Cells
  • Spindle Apparatus / physiology
  • Spindle Apparatus / ultrastructure
  • Spodoptera
  • Staurosporine / pharmacology


  • Cdc20 Proteins
  • Cell Cycle Proteins
  • MAD2L1 protein, human
  • Mad2 Proteins
  • Recombinant Proteins
  • CDC20 protein, human
  • Adenosine Triphosphate
  • BUB1 protein, human
  • Protein Serine-Threonine Kinases
  • Chaperonin Containing TCP-1
  • ATPases Associated with Diverse Cellular Activities
  • TRIP13 protein, human
  • Staurosporine