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Record W3203574804 · doi:10.1126/sciadv.abj2485

GABARAP sequesters the FLCN-FNIP tumor suppressor complex to couple autophagy with lysosomal biogenesis

2021· article· en· W3203574804 on OpenAlexafffund
Jonathan M. Goodwin, Ward G. Walkup, Kirsty M. Hooper, Taoyingnan Li, Chieko Kishi‐Itakura, Aylwin Ng, Timothy Z. Lehmberg, Archana Jha, Sravya Kommineni, Katherine Fletcher, Jorge García‐Fortanet, Yaya Fan, Qing Tang, Menghao Wei, Asmita Agrawal, Sagar R. Budhe, Sreekanth R. Rouduri, Dan Baird, Jeff Saunders, Janna Kiselar, Mark R. Chance, Andrea Ballabio, B.A. Appleton, John H. Brumell, Oliver Florey, Leon O. Murphy

Bibliographic record

VenueScience Advances · 2021
Typearticle
Languageen
FieldMedicine
TopicAutophagy in Disease and Therapy
Canadian institutionsSickKids FoundationHospital for Sick ChildrenUniversity of Toronto
FundersBiotechnology and Biological Sciences Research CouncilCanadian Institutes of Health ResearchNational Institutes of HealthCancer Research UK
KeywordsFolliculinBiogenesisAutophagySuppressorCell biologyChemistryTranscription (linguistics)Transcription factorBiologyBiochemistryGene

Abstract

fetched live from OpenAlex

-induced xenophagy, the membrane conjugation of GABARAP, but not LC3, is required for activation of TFEB/TFE3 to control lysosomal capacity. GABARAP directly binds to a previously unidentified LC3-interacting motif (LIR) in the FLCN/FNIP tumor suppressor complex and mediates sequestration to GABARAP-conjugated membrane compartments. This disrupts FLCN/FNIP GAP function toward RagC/D, resulting in impaired substrate-specific mTOR-dependent phosphorylation of TFEB. Thus, the GABARAP-FLCN/FNIP-TFEB axis serves as a molecular sensor that coordinates lysosomal homeostasis with perturbations and cargo flux within the autophagy-lysosomal network.

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 score0.099
Threshold uncertainty score0.418

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.001
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 head0.022
GPT teacher head0.312
Teacher spread0.290 · 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

Citations126
Published2021
Admission routes2
Has abstractyes

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