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Cell cycle

Signalling to wait

Nature Reviews Molecular Cell Biology volume 10, pages 160–161 (2009)Cite this article

Kulukian et al. purified mitotic checkpoint components and tested their ability to inhibit the ubiquitin ligase activity of APC/CCDC20 in vitro. Increasing amounts of mitotic arrest deficient 2 (MAD2) inhibit APC/CCDC20 activity, and purified chromosomes with unattached kinetochores enhance this effect. Incubation of purified chromosomes with checkpoint components, followed by chromosome removal prior to the addition of APC/C, enhances APC/CCDC20 inhibition. So, unattached kinetochores act on MAD2 to produce a soluble CDC20 inhibitor that enhances mitotic checkpoint signalling.

MAD1 is stably located at unattached kinetochores, and an antibody that prevents the binding of MAD2 to MAD1 (and therefore MAD2 recruitment to unattached kinetochores) blocks the enhancement of APC/CCDC20 inhibition by purified chromosomes. The same is true for MAD2 mutants that bind to MAD1 but are unable to recruit a second MAD2 molecule to form MAD2 dimers. These results suggest that MAD1–MAD2 heterodimers recruit cytosolic MAD2 molecules to unattached kinetochores to enable CDC20 binding.

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References

ORIGINAL RESEARCH PAPERS

  1. Kulukian, A. et al. Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding. Dev. Cell 16, 105–117 (2009)

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  2. Malureanu, L. A. et al. BubR1 N terminus acts as a soluble inhibitor of cyclin B degradation by APC/CCdc20 in interphase. Dev. Cell 16, 118–131 (2009)

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FURTHER READING

  1. Musacchio, A. & Salmon, E. D. The spindle-assembly checkpoint in space and time. Nature Rev. Mol. Cell Biol. 8, 379–393 (2007)

    Article  CAS  Google Scholar 

  2. Peters, J.-M. The anaphase promoting complex/cyclosome: a machine designed to destroy. Nature Rev. Mol. Cell Biol. 7, 644–656 (2006)

    Article  CAS  Google Scholar 

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Authors
  1. Francesca Cesari
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Cesari, F. Signalling to wait. Nat Rev Mol Cell Biol 10, 160–161 (2009). https://doi.org/10.1038/nrm2643

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