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Cell cycle

Finding space in the APC/C

Nature Reviews Molecular Cell Biology volume 13, pages 210–211 (2012)Cite this article

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Mad3 inhibits ... the APC/C by blocking substrate–Cdc20 interactions.

The APC/C is an E3 ubiquitin ligase that targets proteins for degradation and initiates chromosome segregation. The APC/C recognizes its targets through two degradation motifs (degrons) — the destruction (D) box (Arg-Xaa-Xaa-Leu) and the KEN box (Lys-Glu-Asn) — and requires a co-activator, either Cdc20 or Cdc20 homologue 1 (Cdh1), for target recognition. The authors determined the crystal structure of the fission yeast MCC, which comprises Mad2 and Mad3 as well as Cdc20, and identified two conserved surfaces in the WD40 domain of Cdc20 that are responsible for degron recognition: the KEN box receptor and the D box co-receptor sites. Interestingly, a Mad3 amino-terminal KEN box interacted with Cdc20 at the KEN box receptor site, and five conserved residues (Asp180, Asn326, Thr368, Gln392 and Arg438) of Cdc20 were found to be important for this interaction. In addition, an unexpected contact between Cdc20 and the aliphatic side chain of Leu215 of Mad3, which mimics a D box, was described. Importantly, mution of Cdc20 at either the KEN box receptor or the D box co-receptor indicated that residues at these sites are important for substrate recognition by the APC/C.

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References

ORIGINAL RESEARCH PAPER

  1. Chao, W. C. H. et al. Structure of the mitotic checkpoint complex. Nature 21 Mar 2012 (doi:10.1038/nature10896)

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FURTHER READING

  1. Pines, J. Cubism and the cell cycle: the many faces of the APC/C. Nature Rev. Mol. Cell Biol. 12, 427–438 (2011)

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  2. 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 

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Authors
  1. Kim Baumann
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Baumann, K. Finding space in the APC/C. Nat Rev Mol Cell Biol 13, 210–211 (2012). https://doi.org/10.1038/nrm3319

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