ArticleThe Journal of biological chemistry2015
Positive and negative regulation of vertebrate separase by Cdk1-cyclin B1 may explain why securin is dispensable.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- The Small but Versatile Cyclin-Dependent Kinase Subunit CKS: C. elegans CKS-1 Regulates Anaphase Onset and Is Required for Anaphase B During Oocyte Meiosis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Anaphase onset requires CKS-1-mediated destruction of securin in meiosis I and cyclin B1 in meiosis II.The Journal of cell biology · 2026Article
- Securin regulates the spatiotemporal dynamics of separase.The Journal of cell biology · 2025Article
- Positively charged specificity site in cyclin B1 is essential for mitotic fidelity.Nature communications · 2025Article
- Role of chromosomal cohesion and separation in aneuploidy and tumorigenesis.Cellular and molecular life sciences : CMLS · 2024Review
- Hexavalent Chromium Targets Securin to Drive Numerical Chromosome Instability in Human Lung Cells.International journal of molecular sciences · 2023Article
- Securin Regulates the Spatiotemporal Dynamics of Separase.bioRxiv : the preprint server for biology · 2023Article
- Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1.Nature communications · 2023Article
- Meiotic Cell Cycle Progression in Mouse Oocytes: Role of Cyclins.International journal of molecular sciences · 2023Review
- The molecular mechanisms of human separase regulation.Biochemical Society transactions · 2023Review
- Review
- Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase.Cell reports · 2022Article
- Article
- A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes.Nature communications · 2021Article
- Structure and Function of the Separase-Securin Complex.Sub-cellular biochemistry · 2021Review
- Article
- Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.Nature communications · 2019Article
- The Arabidopsis anaphase-promoting complex/cyclosome subunit 8 is required for male meiosis.The New phytologist · 2019Article
- Characterization of a novel separase-interacting protein and candidate new securin, Eip1p, in the fungal pathogenMolecular biology of the cell · 2019Article
- The PSMA8 subunit of the spermatoproteasome is essential for proper meiotic exit and mouse fertility.PLoS genetics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sister chromatid cohesion is established during replication by entrapment of both dsDNAs within the cohesin ring complex. It is dissolved in anaphase when separase, a giant cysteine endopeptidase, cleaves the Scc1/Rad21 subunit of cohesin, thereby triggering chromosome segregation. Separase is held inactive by association with securin until this anaphase inhibitor is destroyed at the metaphase-to-anaphase transition by ubiquitin-dependent degradation. The relevant ubiquitin ligase, the anaphase-promoting complex/cyclosome, also targets cyclin B1, thereby causing inactivation of Cdk1 and mitotic exit. Although separase is essential, securin knock-out mice are surprisingly viable and fertile. Capitalizing on our previous finding that Cdk1-cyclin B1 can also bind and inhibit separase, we investigated whether this kinase might be suitable to maintain faithful timing and execution of anaphase in the absence of securin. We found that, similar to securin, Cdk1-cyclin B1 regulates separase in both a positive and negative manner. Although securin associates with nascent separase to co-translationally assist proper folding, Cdk1-cyclin B1 acts on native state separase. Upon entry into mitosis, Cdk1-cyclin B1-dependent phosphorylation of Ser-1126 renders separase prone to inactivation by aggregation/precipitation. Stable association of Cdk1-cyclin B1 with phosphorylated separase counteracts this tendency and stabilizes separase in an inhibited yet activatable state. These opposing effects are suited to prevent premature cleavage of cohesin in early mitosis while ensuring timely activation of separase by anaphase-promoting complex/cyclosome-dependent degradation of cyclin B1. Coupling sister chromatid separation with subsequent exit from mitosis by this simplified mode might have been the common scheme of mitotic control prior to the evolution of securin.
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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.