Negative feedback at kinetochores underlies a responsive spindle checkpoint signal
| Autor: | Wilco Nijenhuis, Antoinette Teixeira, Adrian T. Saurin, Geert J. P. L. Kops, Giulia Vallardi |
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| Rok vydání: | 2014 |
| Předmět: |
Amino Acid Motifs
Aurora B kinase Cell Cycle Proteins Smad2 Protein Spindle Apparatus Protein Serine-Threonine Kinases Editorials: Cell Cycle Features Biology Microtubules Chromosome segregation chemistry.chemical_compound Microtubule Cell Line Tumor Chromosome Segregation Aurora Kinase B Humans Protein Phosphatase 2 Phosphorylation RNA Small Interfering Kinetochores Mitosis Feedback Physiological Kinetochore Nocodazole Cell Biology Protein-Tyrosine Kinases Tubulin Modulators Protein Structure Tertiary Spindle apparatus Cell biology Spindle checkpoint chemistry embryonic structures M Phase Cell Cycle Checkpoints RNA Interference Microtubule-Associated Proteins HeLa Cells Protein Binding Signal Transduction |
| Zdroj: | Nature Cell Biology. 16:1257-1264 |
| ISSN: | 1476-4679 1465-7392 |
| Popis: | Kinetochores are specialized multi-protein complexes that play a crucial role in maintaining genome stability. They bridge attachments between chromosomes and microtubules during mitosis and they activate the spindle assembly checkpoint (SAC) to arrest division until all chromosomes are attached. Kinetochores are able to efficiently integrate these two processes because they can rapidly respond to changes in microtubule occupancy by switching localized SAC signalling ON or OFF. We show that this responsiveness arises because the SAC primes kinetochore phosphatases to induce negative feedback and silence its own signal. Active SAC signalling recruits PP2A-B56 to kinetochores where it antagonizes Aurora B to promote PP1 recruitment. PP1 in turn silences the SAC and delocalizes PP2A-B56. Preventing or bypassing key regulatory steps demonstrates that this spatiotemporal control of phosphatase feedback underlies rapid signal switching at the kinetochore by: allowing the SAC to quickly transition to the ON state in the absence of antagonizing phosphatase activity; and ensuring phosphatases are then primed to rapidly switch the SAC signal OFF when kinetochore kinase activities are diminished by force-producing microtubule attachments. |
| Databáze: | OpenAIRE |
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