The Bcl‐2 family members Mcl‐1 and Bim modulate apoptosis in glutamine‐deprived Sp2/0‐Ag14 mouse cells
Bibliographic record
Abstract
In highly proliferating cells, metabolic reprogramming results in a cellular dependence toward L‐glutamine (Gln), a phenomenon of marked therapeutic interest. However, the molecular events linking Gln to cell survival are still poorly defined. Our group has shown that Sp2/0‐Ag14 (Sp2/0) cells are acutely sensitive to Gln starvation, undergoing apoptosis via the intrinsic pathway after only 2 hours of Gln deprivation. The current study examined the relative contribution of proteins of the Bcl‐2 family in this phenomenon. Immunoblotting revealed that Mcl‐1, Bax, Bim and Puma are the major Bcl‐2 family proteins expressed in Sp2/0 cells. While Sp2/0 cells with an RNAi‐induced decrease in Puma levels behaved like the wild‐type cell line, reducing Bim expression led to a significant increase in cell survival following Gln deprivation. Western blot analysis revealed that Gln starvation did not affect Bim levels, but did lead to a reduction in Mcl‐1. We found that Sp2/0 cells are highly sensitive to obatoclax, a Mcl‐1‐specific chemical inhibitor. Furthermore, obatoclax increased the sensitivity of Sp2/0 cells to glutamine starvation, an effect prevented by the constitutive expression of Bcl‐xL (which is not targeted by the drug). All together, our data place Mcl‐1 and Bim at the core of the apoptotic machinery triggered by Gln starvation in Sp2/0 cells. Funded by NSERC‐CANADA (to ERG).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".