The Mitotic Checkpoint Complex Requires an Evolutionary Conserved Cassette to Bind and Inhibit Active APC/C.
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Date
2016-12-15Author
Di Fiore, B
Wurzenberger, C
Davey, NE
Pines, J
Type
Journal Article
Metadata
Show full item recordAbstract
The Spindle Assembly Checkpoint (SAC) ensures genomic stability by preventing sister chromatid separation until all chromosomes are attached to the spindle. It catalyzes the production of the Mitotic Checkpoint Complex (MCC), which inhibits Cdc20 to inactivate the Anaphase Promoting Complex/Cyclosome (APC/C). Here we show that two Cdc20-binding motifs in BubR1 of the recently identified ABBA motif class are crucial for the MCC to recognize active APC/C-Cdc20. Mutating these motifs eliminates MCC binding to the APC/C, thereby abolishing the SAC and preventing cells from arresting in response to microtubule poisons. These ABBA motifs flank a KEN box to form a cassette that is highly conserved through evolution, both in the arrangement and spacing of the ABBA-KEN-ABBA motifs, and association with the amino-terminal KEN box required to form the MCC. We propose that the ABBA-KEN-ABBA cassette holds the MCC onto the APC/C by binding the two Cdc20 molecules in the MCC-APC/C complex.
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Subject
Hela Cells
Animals
Ciona intestinalis
Humans
Drosophila melanogaster
Caenorhabditis elegans
Arabidopsis
Protein-Serine-Threonine Kinases
Sequence Alignment
Gene Expression
Amino Acid Motifs
Conserved Sequence
Sequence Homology, Amino Acid
Mutation
Biological Evolution
Time-Lapse Imaging
M Phase Cell Cycle Checkpoints
Anaphase-Promoting Complex-Cyclosome
Cdc20 Proteins
Language
eng
Date accepted
2016-10-31
License start date
2016-12-08
Citation
Molecular cell, 2016, 64 (6), pp. 1144 - 1153
Publisher
CELL PRESS