ArticleCell cycle (Georgetown, Tex.)2016
Spatial regulation of greatwall by Cdk1 and PP2A-Tws in the cell cycle.
Article in Cell cycle (Georgetown, Tex.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Article
- The ATM-E6AP-MASTL axis mediates DNA damage checkpoint recovery.bioRxiv : the preprint server for biology · 2023Article
- Spatiotemporal coordination of Greatwall-Endos-PP2A promotes mitotic progression.The Journal of cell biology · 2021Article
- Article
- MASTL promotes cell contractility and motility through kinase-independent signaling.The Journal of cell biology · 2020Article
- Molecular Basis of the Mechanisms Controlling MASTL.Molecular & cellular proteomics : MCP · 2020Article
- Greatwall-Endosulfine: A Molecular Switch that Regulates PP2A/B55 Protein Phosphatase Activity in Dividing and Quiescent Cells.International journal of molecular sciences · 2019Review
- Cdc14 activation requires coordinated Cdk1-dependent phosphorylation of Net1 and PP2A-Cdc55 at anaphase onset.Cellular and molecular life sciences : CMLS · 2019Article
- Transcriptome analysis of pancreatic cancer cell response to treatment with grape seed proanthocyanidins.Oncology letters · 2019Article
- Protein interactomes of protein phosphatase 2A B55 regulatory subunits reveal B55-mediated regulation of replication protein A under replication stress.Scientific reports · 2018Article
- Coordination of Protein Kinase and Phosphoprotein Phosphatase Activities in Mitosis.Frontiers in cell and developmental biology · 2018Review
- Coupling of Polo kinase activation to nuclear localization by a bifunctional NLS is required during mitotic entry.Nature communications · 2017Article
- Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B.The Journal of biological chemistry · 2017Article
- Article
- A STRIPAK complex mediates axonal transport of autophagosomes and dense core vesicles through PP2A regulation.The Journal of cell biology · 2017Article
- The broken "Off" switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance.BBA clinical · 2016Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Entry into mitosis requires the phosphorylation of multiple substrates by cyclin B-Cdk1, while exit from mitosis requires their dephosphorylation, which depends largely on the phosphatase PP2A in complex with its B55 regulatory subunit (Tws in Drosophila). At mitotic entry, cyclin B-Cdk1 activates the Greatwall kinase, which phosphorylates Endosulfine proteins, thereby activating their ability to inhibit PP2A-B55 competitively. The inhibition of PP2A-B55 at mitotic entry facilitates the accumulation of phosphorylated Cdk1 substrates. The coordination of these enzymes involves major changes in their localization. In interphase, Gwl is nuclear while PP2A-B55 is cytoplasmic. We recently showed that Gwl suddenly relocalizes from the nucleus to the cytoplasm in prophase, before nuclear envelope breakdown and that this controlled localization of Gwl is required for its function. We and others have shown that phosphorylation of Gwl by cyclin B-Cdk1 at multiple sites is required for its nuclear exclusion, but the precise mechanisms remained unclear. In addition, how Gwl returns to its nuclear localization was not explored. Here we show that cyclin B-Cdk1 directly inactivates a Nuclear Localization Signal in the central region of Gwl. This phosphorylation facilitates the cytoplasmic retention of Gwl, which is exported to the cytoplasm in a Crm1-dependent manner. In addition, we show that PP2A-Tws promotes the return of Gwl to its nuclear localization during cytokinesis. Our results indicate that the cyclic changes in Gwl localization at mitotic entry and exit are directly regulated by the antagonistic cyclin B-Cdk1 and PP2A-Tws enzymes.
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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.