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Intracellular localization of TDAG51 modulates its effect on cell death

2009· article· en· W2276975798 on OpenAlexafffund
Hiam Al‐Bayati, Jeffrey G. Dickhout, Ray Traunt, Richard C. Austin

Bibliographic record

VenueThe FASEB Journal · 2009
Typearticle
Languageen
FieldMedicine
TopicCell Adhesion Molecules Research
Canadian institutionsMcMaster UniversitySt. Joseph’s Healthcare Hamilton
FundersCanadian Institutes of Health Research
KeywordsIntracellularNuclear localization sequenceProgrammed cell deathCell biologyCytoplasmBiologyNLSTransfectionNuclear transportCell nucleusCellApoptosisCell cultureGenetics

Abstract

fetched live from OpenAlex

Our previously findings indicate that T‐cell death associated gene 51 (TDAG51) contributes to cell death in atherosclerotic lesions. To determine if these cell death effects are mediated by TDAG51 intracellular localization, we performed sequence analysis of the TDAG51 cDNA to identify novel cellular targeting domains. This analysis revealed two putative motifs; a nuclear exiting signal (NES) (70‐vasleppvkl‐80) and nuclear localization signal (NLS) (16‐krsdgllqlwkkk‐28). We hypothesized that these TDAG51 motifs play a critical role in its intracellular transport, thereby modulating its pro‐apoptotic effects. To investigate this phenomenon, VKL was mutated to AKA in NES to impair exiting of the TDAG51 protein from the nucleus to the cytoplasm and WKKK was mutated to WKAA in NLS to impair entrance of TDAG51 into the nucleus. Following transient transfection of the fused GFP constructs into HeLa cells, the cellular localization of these mutant TDAG51 proteins was assessed using confocal microscopy on fixed cells or visualized in living cells over a 2 to 48 hour time period. Our findings show that both motifs are involved in the intracellular transport of TDAG51. By determining cell viability, we were able to determine the predominant effects of nuclear TDAG51 on cell death. These studies provide a better understanding of the cellular motifs in TDAG51 that contribute to cell death. Supported by the CIHR (MOP‐74477).

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 score0.002
Threshold uncertainty score0.007

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.018
GPT teacher head0.287
Teacher spread0.268 · 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
Published2009
Admission routes2
Has abstractyes

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