ArticlePloS one2012
Cohesion fatigue explains why pharmacological inhibition of the APC/C induces a spindle checkpoint-dependent mitotic arrest.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase.Developmental cell · 2021Article
- APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis.Seminars in cancer biology · 2020Review
- ProTAME Arrest in Mammalian Oocytes and Embryos Does Not Require Spindle Assembly Checkpoint Activity.International journal of molecular sciences · 2019Article
- Aurora B kinase activity-dependent and -independent functions of the chromosomal passenger complex in regulating sister chromatid cohesion.The Journal of biological chemistry · 2019Article
- A positive feedback mechanism ensures proper assembly of the functional inner centromere during mitosis in human cells.The Journal of biological chemistry · 2019Article
- Atypical APC/C-dependent degradation of Mcl-1 provides an apoptotic timer during mitotic arrest.The EMBO journal · 2018Article
- Multiple determinants and consequences of cohesion fatigue in mammalian cells.Molecular biology of the cell · 2018Article
- Non-random Mis-segregation of Human Chromosomes.Cell reports · 2018Article
- Peptide inhibitors of the anaphase promoting-complex that cause sensitivity to microtubule poison.PloS one · 2018Article
- Review
- Mechanisms and consequences of aneuploidy and chromosome instability in the aging brain.Mechanisms of ageing and development · 2017Review
- Observing Mitotic Division and Dynamics in a Live Zebrafish Embryo.Journal of visualized experiments : JoVE · 2016Article
- The Spindle Assembly Checkpoint Is Not Essential for Viability of Human Cells with Genetically Lowered APC/C Activity.Cell reports · 2016Article
- Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524.eLife · 2016Article
- Mcl-1 dynamics influence mitotic slippage and death in mitosis.Oncotarget · 2016Article
- Defective sister chromatid cohesion is synthetically lethal with impaired APC/C function.Nature communications · 2015Article
- Cenp-E inhibitor GSK923295: Novel synthetic route and use as a tool to generate aneuploidy.Oncotarget · 2015Article
- Spatiotemporal regulation of the anaphase-promoting complex in mitosis.Nature reviews. Molecular cell biology · 2015Review
- SNW1 enables sister chromatid cohesion by mediating the splicing of sororin and APC2 pre-mRNAs.The EMBO journal · 2014Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Spindle Assembly Checkpoint (SAC) delays the onset of anaphase in response to unattached kinetochores by inhibiting the activity of the Anaphase-Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. Once all the chromosomes have bioriented, SAC signalling is somehow silenced, which allows progression through mitosis. Recent studies suggest that the APC/C itself participates in SAC silencing by targeting an unknown factor for proteolytic degradation. Key evidence in favour of this model comes from the use of proTAME, a small molecule inhibitor of the APC/C. In cells, proTAME causes a mitotic arrest that is SAC-dependent. Even though this observation comes at odds with the current view that the APC/C acts downstream of the SAC, it was nonetheless argued that these results revealed a role for APC/C activity in SAC silencing. However, we show here that the mitotic arrest induced by proTAME is due to the induction of cohesion fatigue, a phenotype that is caused by the loss of sister chromatid cohesion following a prolonged metaphase. Under these conditions, the SAC is re-activated and APC/C inhibition is maintained independently of proTAME. Therefore, these results provide a simpler explanation for why the proTAME-induced mitotic arrest is also dependent on the SAC. While these observations question the notion that the APC/C is required for SAC silencing, we nevertheless show that APC/C activity does partially contribute to its own release from inhibitory complexes, and importantly, this does not depend on proteasome-mediated degradation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.