Hexokinase 2 controls cellular stress response through localization of an RNA-binding protein
Bibliographic record
Abstract
Subcellular localization of RNA-binding proteins is a key determinant of their ability to control RNA metabolism and cellular stress response. Using an RNAi-based kinome-wide screen, we identified hexokinase 2 (HK2) as a regulator of the cytoplasmic accumulation of hnRNP A1 in response to hypertonic stress and human rhinovirus infection (HRV). We show that inhibition of HK2 expression or pharmacological inhibition of HK2 activity blocks the cytoplasmic accumulation of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), restores expression of B-cell lymphoma-extra large (Bcl-xL), and protects cells against hypertonic stress-induced apoptosis. Reduction of HK2 protein levels by knockdown results in decreased HRV replication, a delay in HRV-induced cell death, and a reduced number of infected cells, all of which can be rescued by forced expression of a cytoplasm-restricted hnRNP A1. Our data elucidate a novel role for HK2 in cellular stress response and viral infection that could be exploited for therapeutic intervention.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".