The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators

Dev Cell. 2015 Feb 9;32(3):358-372. doi: 10.1016/j.devcel.2015.01.003.

Abstract

The anaphase-promoting complex or cyclosome (APC/C) is the ubiquitin ligase that regulates mitosis by targeting specific proteins for degradation at specific times under the control of the spindle assembly checkpoint (SAC). How the APC/C recognizes its different substrates is a key problem in the control of cell division. Here, we have identified the ABBA motif in cyclin A, BUBR1, BUB1, and Acm1, and we show that it binds to the APC/C coactivator CDC20. The ABBA motif in cyclin A is required for its proper degradation in prometaphase through competing with BUBR1 for the same site on CDC20. Moreover, the ABBA motifs in BUBR1 and BUB1 are necessary for the SAC to work at full strength and to recruit CDC20 to kinetochores. Thus, we have identified a conserved motif integral to the proper control of mitosis that connects APC/C substrate recognition with the SAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Cdc20 Proteins / metabolism*
  • Cell Cycle / physiology
  • Humans
  • Kinetochores / metabolism
  • Membrane Proteins / metabolism*
  • Microfilament Proteins / metabolism*
  • Mitosis / physiology*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / metabolism*
  • Ubiquitin-Protein Ligase Complexes / metabolism*

Substances

  • Cdc20 Proteins
  • MTSS2 protein, human
  • Membrane Proteins
  • Microfilament Proteins
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • BUB1 protein, human
  • Protein-Serine-Threonine Kinases