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Record W3136855762 · doi:10.1038/s41467-021-21922-w

Bora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry

2021· article· en· W3136855762 on OpenAlexafffund
Nicolas Tavernier, Y. Thomas, Suzanne Vigneron, Pierre Maisonneuve, Stephen Orlicky, P. Mäder, Saroj G. Regmi, Lucie Van Hove, Nicholas M. Levinson, Geneviève M. C. Gasmi-Seabrook, Nicolas Joly, Marion Poteau, Griselda Vélez‐Aguilera, Olivier Gavet, Anna Castro, Mary Dasso, Thierry Lorca, Frank Sicheri, Lionel Pintard

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMicrotubule and mitosis dynamics
Canadian institutionsUniversity of TorontoUniversity Health NetworkCanada Research ChairsPrincess Margaret Cancer CentreSinai Health SystemLunenfeld-Tanenbaum Research Institute
FundersCanadian Cancer Society Research InstituteUniversité de ParisCanadian Institutes of Health ResearchTerry Fox Research InstituteConsejo Nacional de Ciencia y TecnologíaAgence Nationale de la RechercheFondation ARC pour la Recherche sur le CancerUniversity of TorontoFondation pour la Recherche MédicaleLaboratoire d'Excellence EpiGenMedInfrastructures en Biologie Santé et AgronomiePrincess Margaret Cancer Foundation
KeywordsPhosphorylationPLK1XenopusSerineMitosisKinaseCyclin-dependent kinase 1Cell biologyPhosphoserineActivator (genetics)Protein kinase domainBiologyBiochemistryMutantCell cycleReceptor

Abstract

fetched live from OpenAlex

Polo-like kinase 1 (Plk1) is instrumental for mitotic entry and progression. Plk1 is activated by phosphorylation on a conserved residue Thr210 in its activation segment by the Aurora A kinase (AURKA), a reaction that critically requires the co-factor Bora phosphorylated by a CyclinA/B-Cdk1 kinase. Here we show that phospho-Bora is a direct activator of AURKA kinase activity. We localize the key determinants of phospho-Bora function to a 100 amino acid region encompassing two short Tpx2-like motifs and a phosphoSerine-Proline motif at Serine 112, through which Bora binds AURKA. The latter substitutes in trans for the Thr288 phospho-regulatory site of AURKA, which is essential for an active conformation of the kinase domain. We demonstrate the importance of these determinants for Bora function in mitotic entry both in Xenopus egg extracts and in human cells. Our findings unveil the activation mechanism of AURKA that is critical for mitotic entry.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.333
Threshold uncertainty score0.600

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.012
GPT teacher head0.281
Teacher spread0.269 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations47
Published2021
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicMicrotubule and mitosis dynamicsFrench-language works237,207