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Record W4386935335 · doi:10.1038/s41467-023-41067-2

The NCOR-HDAC3 co-repressive complex modulates the leukemogenic potential of the transcription factor ERG

2023· article· en· W4386935335 on OpenAlexafffund
Eitan Kugler, Shreyas Madiwale, Darren Yong, Julie A.I. Thoms, Yehudit Birger, David B. Sykes, Johannes Schmoellerl, Aneta Drakul, Valdemar Priebe, Muhammad Yassin, Nasma Aqaqe, Avigail Rein, Hila Fishman, Ifat Geron, Chun‐Wei Chen, Brian Raught, Qiao Liu, Heather Ogana, Elisabeth Liedke, Jean‐Pierre Bourquin, Johannes Zuber, Michael Milyavsky, John E. Pimanda, Gilbert G. Privé, Shai Izraeli

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHistone Deacetylase Inhibitors Research
Canadian institutionsPrincess Margaret Cancer CentreUniversity of TorontoUniversity Health Network
FundersCanadian Institutes of Health ResearchIsrael Science FoundationWeizmann Institute of Science
KeywordsHDAC3ErgTranscription factorCancer researchBiologyCell biologyETS transcription factor familyRepressorMyeloid leukemiaHaematopoiesisGeneticsGeneHistoneStem cellHistone deacetylaseBiochemistryRetinal

Abstract

fetched live from OpenAlex

The ERG (ETS-related gene) transcription factor is linked to various types of cancer, including leukemia. However, the specific ERG domains and co-factors contributing to leukemogenesis are poorly understood. Drug targeting a transcription factor such as ERG is challenging. Our study reveals the critical role of a conserved amino acid, proline, at position 199, located at the 3' end of the PNT (pointed) domain, in ERG's ability to induce leukemia. P199 is necessary for ERG to promote self-renewal, prevent myeloid differentiation in hematopoietic progenitor cells, and initiate leukemia in mouse models. Here we show that P199 facilitates ERG's interaction with the NCoR-HDAC3 co-repressor complex. Inhibiting HDAC3 reduces the growth of ERG-dependent leukemic and prostate cancer cells, indicating that the interaction between ERG and the NCoR-HDAC3 co-repressor complex is crucial for its oncogenic activity. Thus, targeting this interaction may offer a potential therapeutic intervention.

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 score0.001
Threshold uncertainty score0.005

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)0.0010.000

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 head0.028
GPT teacher head0.334
Teacher spread0.305 · 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

Citations5
Published2023
Admission routes2
Has abstractyes

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