Evidence map›Paper›PMID 27889260›Full record

ArticleCurrent biology : CB2016

Two Bistable Switches Govern M Phase Entry.

Satoru Mochida, Scott Rata, Hirotsugu Hino, Takeharu Nagai, Béla Novák

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 89 citations in OpenAlex.

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  13. On the assembly of the mitotic spindle, bistability and hysteresis.Cellular and molecular life sciences : CMLS · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Satoru MochidaPriority Organization for Innovation and Excellence, Kumamoto University, Kyoyoto-honjo 1, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan; Institute for Medical Embryology and Genetics, Kumamoto University, Kyoyoto-honjo 1, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan; International Research Center for Medical Science, Kumamoto University, Kyoyoto-honjo 1, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan; Precursory Research for Embryonic Science and Technology (PRESTO) Program, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: mochida@kumamoto-u.ac.jp.
Scott RataDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
Hirotsugu HinoPriority Organization for Innovation and Excellence, Kumamoto University, Kyoyoto-honjo 1, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
Takeharu NagaiThe Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047, Japan.
Béla NovákDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK. Electronic address: bela.novak@bioch.ox.ac.uk.
Kumamoto University · JPUniversity of Oxford · GBOsaka University · JP

Funding

Biotechnology and Biological Sciences Research Council BB/MM00354X/1
6 · The paper itself

Abstract

The abrupt and irreversible transition from interphase to M phase is essential to separate DNA replication from chromosome segregation. This transition requires the switch-like phosphorylation of hundreds of proteins by the cyclin-dependent kinase 1 (Cdk1):cyclin B (CycB) complex. Previous studies have ascribed these switch-like phosphorylations to the auto-activation of Cdk1:CycB through the removal of inhibitory phosphorylations on Cdk1-Tyr15 [1, 2]. The positive feedback in Cdk1 activation creates a bistable switch that makes mitotic commitment irreversible [2-4]. Here, we surprisingly find that Cdk1 auto-activation is dispensable for irreversible, switch-like mitotic entry due to a second mechanism, whereby Cdk1:CycB inhibits its counteracting phosphatase (PP2A:B55). We show that the PP2A:B55-inhibiting Greatwall (Gwl)-endosulfine (ENSA) pathway is both necessary and sufficient for switch-like phosphorylations of mitotic substrates. Using purified components of the Gwl-ENSA pathway in a reconstituted system, we found a sharp Cdk1 threshold for phosphorylation of a luminescent mitotic substrate. The Cdk1 threshold to induce mitotic phosphorylation is distinctly higher than the Cdk1 threshold required to maintain these phosphorylations-evidence for bistability. A combination of mathematical modeling and biochemical reconstitution show that the bistable behavior of the Gwl-ENSA pathway emerges from its mutual antagonism with PP2A:B55. Our results demonstrate that two interlinked bistable mechanisms provide a robust solution for irreversible and switch-like mitotic entry.

Indexed as

AnimalsCDC2 Protein KinaseCell Cycle CheckpointsCell DivisionGene Expression Regulation, EnzymologicIntercellular Signaling Peptides and ProteinsModels, BiologicalPeptidesPhosphorylationProtein Phosphatase 2Signal TransductionCDC2 Protein KinaseendosulfineIntercellular Signaling Peptides and ProteinsPeptidesProtein Phosphatase 2cyclin-dependent kinaseGreatwall kinasehysteresismitosisPP2Arobustnessthreshold

Identifiers

PMID27889260
PMCPMC5196020
OpenAlexW2552631918

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.