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Record W2734479613 · doi:10.1073/pnas.1705304114

mTORC1 activates SREBP-2 by suppressing cholesterol trafficking to lysosomes in mammalian cells

2017· article· en· W2734479613 on OpenAlex
Walaa Eid, Kristin Dauner, Kevin C. Courtney, AnneMarie Gagnon, Robin J. Parks, Alexander Sorisky, Xiaohui Zha

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2017
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCellular transport and secretion
Canadian institutionsOttawa HospitalUniversity of Ottawa
FundersCanadian Institutes of Health ResearchGovernment of Canada
KeywordsmTORC1Sterol regulatory element-binding proteinGolgi apparatusEndoplasmic reticulumNPC1Cell biologyEndosomeCholesterolChemistryTranscription factorAutophagyBiologySterolBiochemistrySignal transductionPI3K/AKT/mTOR pathwayGene

Abstract

fetched live from OpenAlex

Significance Through unknown mechanisms mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi to produce mature SREBP-2, which translocates to the nucleus to act as a transcription factor. Low ER cholesterol is a well-known inducer of SREBP-2 activation. We thus investigated whether mTORC1 activates SREBP-2 by reducing ER cholesterol levels. We report that, in cultured mammalian cells, an increase in mTORC1 activity is accompanied by a decrease in ER cholesterol and by SREBP-2 activation. Conversely, a decrease in mTORC1 activity coincides with higher ER cholesterol and lower SERBP-2 activity. We demonstrate that, by suppressing autophagy and by maintaining endosomal recycling, mTORC1 actively prevents membrane-derived cholesterol from reaching lysosomes, thereby reducing cholesterol ER and activating SREBP-2.

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.

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 score0.060
Threshold uncertainty score0.226

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 science0.0010.000
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 head0.024
GPT teacher head0.287
Teacher spread0.263 · 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