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Record W4312138534 · doi:10.1101/2022.12.23.521717

NEK10 tyrosine phosphorylates β-catenin to regulate its cytoplasmic turnover

2022· preprint· en· W4312138534 on OpenAlexaff
Previn Dutt, Nasir Haider, Samar Mouaaz, Lauren Podmore, Vuk Stambolic

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicWnt/β-catenin signaling in development and cancer
Canadian institutionsUniversity of TorontoPrincess Margaret Cancer CentreUniversity Health Network
Fundersnot available
KeywordsPhosphorylationCell biologyKinaseAdherens junctionDNA damageSerineBiologyG2-M DNA damage checkpointp38 mitogen-activated protein kinasesChemistryMAPK/ERK pathwayCell cycle checkpointCell cycleBiochemistryDNAApoptosisCadherinCell

Abstract

fetched live from OpenAlex

Abstract Nek kinases are involved in regulating several different elements of the centrosomal cycle, primary cilia function, and DNA damage responses. Unlike the other members of the Nek family, which are serine-threonine kinases, Nek10 preferentially targets tyrosines. Nek10 appears to have a broad role in DNA damage responses, regulating a MAPK-activated G2/M checkpoint following UV irradiation and influencing the p53-mediated activation induced by genotoxicity. In an attempt to identify additional Nek10 functions, we characterized the effect of Nek10 deletion in lung cancer cells, where it is relatively highly expressed. Nek10 absence led to an increase in both the signaling and adherens junctions pools of β-catenin. Mechanistically, Nek10 associates with the Axin complex where it phosphorylates β-catenin at Tyr30, located within the regulatory region governing β-catenin turnover. In the absence of Nek10 phosphorylation, GSK3-mediated phosphorylation of β-catenin, a prerequisite for its turnover, was significantly impaired. Stabilization of β-catenin driven by Nek10 loss diminished the ability of cells to form tumorspheres in suspension, grow in soft agar, and colonize mouse lung tissue following tail vein injections.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

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)0.0030.001

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 head0.010
GPT teacher head0.219
Teacher spread0.208 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2022
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicWnt/β-catenin signaling in development and cancer→French-language works237,207→