ArticleThe EMBO journal2014
PP2A delays APC/C-dependent degradation of separase-associated but not free securin.
Article in The EMBO journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
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- A murine cytomegalovirus cell cycle regulator (m54.5p) evolved within the conserved viral DNA polymerase gene.PLoS pathogens · 2026Article
- Chromosome segregation synchrony inbioRxiv : the preprint server for biology · 2026Article
- Securin regulates the spatiotemporal dynamics of separase.The Journal of cell biology · 2025Article
- Emerging Roles of PTTG1/Securin in Breast Cancer.Journal of Cancer · 2025Review
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- Securin Regulates the Spatiotemporal Dynamics of Separase.bioRxiv : the preprint server for biology · 2023Article
- Biallelic MAD2L1BP (p31comet) mutation is associated with mosaic aneuploidy and juvenile granulosa cell tumors.JCI insight · 2023Article
- The molecular mechanisms of human separase regulation.Biochemical Society transactions · 2023Review
- Separase and Roads to Disengage Sister Chromatids during Anaphase.International journal of molecular sciences · 2023Review
- Control of protein stability by post-translational modifications.Nature communications · 2023Review
- Review
- 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
- Review
- Ordered dephosphorylation initiated by the selective proteolysis of cyclin B drives mitotic exit.eLife · 2020Article
- Article
- Article
- Review
- Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.Nature communications · 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
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The universal triggering event of eukaryotic chromosome segregation is cleavage of centromeric cohesin by separase. Prior to anaphase, most separase is kept inactive by association with securin. Protein phosphatase 2A (PP2A) constitutes another binding partner of human separase, but the functional relevance of this interaction has remained enigmatic. We demonstrate that PP2A stabilizes separase-associated securin by dephosphorylation, while phosphorylation of free securin enhances its polyubiquitylation by the ubiquitin ligase APC/C and proteasomal degradation. Changing PP2A substrate phosphorylation sites to alanines slows degradation of free securin, delays separase activation, lengthens early anaphase, and results in anaphase bridges and DNA damage. In contrast, separase-associated securin is destabilized by introduction of phosphorylation-mimetic aspartates or extinction of separase-associated PP2A activity. G2- or prometaphase-arrested cells suffer from unscheduled activation of separase when endogenous securin is replaced by aspartate-mutant securin. Thus, PP2A-dependent stabilization of separase-associated securin prevents precocious activation of separase during checkpoint-mediated arrests with basal APC/C activity and increases the abruptness and fidelity of sister chromatid separation in anaphase.
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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.