TDAG51 overexpression mediates proximal tubule epithelial cell apoptosis through its accumulation in the nucleus
Bibliographic record
Abstract
T‐cell death associated gene 51 (TDAG51) overexpression induces apoptosis in many cell types. Sequence analysis revealed that TDAG51 contains a putative nuclear export signal (NES), 78 VASLEPPVKL 87 . We hypothesize that TDAG51‐induced apoptosis is mediated through its nuclear accumulation. Leptomycin B (LMB) was employed to inhibit the nuclear export of TDAG51 in HK2 cells, a proximal tubule cell line. An EC50 of 0.8 ng/mL for LMB was calculated using the known NES of Protein Kinase A Inhibitior (PKI). Doses of 0, 1 and 5 ng/mL LMB were applied to determine any increase in TDAG51 nuclear localization. Apoptotic cell death was evaluated with TUNEL assays and nuclear to cytoplasmic ratios of TDAG51 expression were measured confocally. Both 1 and 5 ng/mL LMB induced nuclear localization of TDAG51 endogenously or ectopically expressed. The 1 ng/mL dose of LMB resulted in significantly greater apoptotic cell death in TDAG51‐transfected HK2 cells than in GFP controls. However, the 5 ng/ml dose of LMB caused an increase in apoptosis independent of TDAG51 overexpression. We assessed nuclear localization of TDAG51 under Staurosporine (STS) stimuli. Treatment with 2 μM STS showed a significant increase in apoptosis and nuclear to cytoplasmic ratios compared to vehicle‐treated controls. Our results demonstrate an increase in the nuclear accumulation of TDAG51 under apoptotic conditions. Supported by the CIHR, MOP‐67116 .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot 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.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
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".