How cyclin A destruction escapes the spindle assembly checkpoint.

The anaphase-promoting complex/cyclosome (APC/C) is the ubiquitin ligase essential to mitosis, which ensures that specific proteins are degraded at specific times to control the order of mitotic events. The APC/C coactivator, Cdc20, is targeted by the spindle assembly checkpoint (SAC) to restrict APC/C activity until metaphase, yet early substrates, such ...
as cyclin A, are degraded in the presence of the active checkpoint. Cdc20 and the cyclin-dependent kinase cofactor, Cks, are required for cyclin A destruction, but how they enable checkpoint-resistant destruction has not been elucidated. In this study, we answer this problem: we show that the N terminus of cyclin A binds directly to Cdc20 and with sufficient affinity that it can outcompete the SAC proteins. Subsequently, the Cks protein is necessary and sufficient to promote cyclin A degradation in the presence of an active checkpoint by binding cyclin A-Cdc20 to the APC/C.
Mesh Terms:
Animals, Carrier Proteins, Cell Cycle, Cell Cycle Proteins, Cyclin A, Cyclin-Dependent Kinases, HeLa Cells, Humans, Mitotic Spindle Apparatus, Protein Binding, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Recombinant Fusion Proteins, Ubiquitin-Protein Ligase Complexes, Ubiquitination
J. Cell Biol.
Date: Aug. 23, 2010
Download Curated Data For This Publication
127631
Switch View:
  • Interactions 9