Akt Determines Cell Fate Through Inhibition of the PERK-eIF2α Phosphorylation Pathway
Why this work is in the frame
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Bibliographic record
Abstract
Metazoans respond to various forms of environmental stress by inducing the phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α) at serine-51, a modification that leads to global inhibition of mRNA translation. We demonstrate induction of the phosphorylation of eIF2α in mammalian cells after either pharmacological inhibition of the phosphoinositide 3-kinase (PI3K)-Akt pathway or genetic or small interfering RNA-mediated ablation of Akt. This increase in the extent of eIF2α phosphorylation also occurred in Drosophila cells and depended on the endoplasmic reticulum (ER)-resident protein kinase PERK, which was inhibited by Akt-dependent phosphorylation at threonine-799. The activity of PERK and the abundance of phosphorylated eIF2α (eIF2αP) were reduced in mouse mammary gland tumors that contained activated Akt, as well as in cells exposed to ER stress or oxidative stress. In unstressed cells, the PERK-eIF2αP pathway mediated survival and facilitated adaptation to the deleterious effects of the inactivation of PI3K or Akt. Inactivation of the PERK-eIF2αP pathway increased the susceptibility of tumor cells to death by pharmacological inhibitors of PI3K or Akt. Thus, we suggest that the PERK-eIF2αP pathway provides a link between Akt signaling and translational control, which has implications for tumor formation and treatment.
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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 | 0.000 | 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 | 0.000 |
| 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 it