Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint.

The spindle assembly checkpoint (SAC) delays progression into anaphase until all chromosomes have aligned on the metaphase plate by inhibiting Cdc20, the mitotic co-activator of the APC/C. Mad2 and BubR1 bind and inhibit Cdc20, thereby forming the mitotic checkpoint complex (MCC), which can bind stably to the APC/C. Whether MCC ...
formation per se is sufficient for a functional SAC or MCC association with the APC/C is required remains unclear. Here, we analyze the role of two conserved motifs in Cdc20, IR and C-Box, in binding of the MCC to the APC/C. Mutants in both motifs assemble the MCC normally, but IR motif integrity is particularly important for stable binding to the APC/C. Cells expressing Cdc20 with a mutated IR motif have a compromised SAC, as uninhibited Cdc20 can compete with the MCC for APC/C binding and activate it. We thus show that stable MCC association with the APC/C is critical for a functional SAC.
Mesh Terms:
Amino Acid Motifs, Anaphase-Promoting Complex-Cyclosome, Binding Sites, Cdc20 Proteins, Conserved Sequence, HeLa Cells, Humans, M Phase Cell Cycle Checkpoints, Mad2 Proteins, Protein Binding, Protein-Serine-Threonine Kinases, Spindle Apparatus
EMBO Rep.
Date: Mar. 01, 2014
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