Insights on Regulation and Function of the Iron Regulatory Protein 1 (IRP1)
Bibliographic record
Abstract
Iron regulatory protein 1 (IRP1) controls the translation or stability of several mRNAs by binding to iron responsive elements (IREs) within their untranslated regions. Its activity is regulated by an unusual iron-sulfur cluster (ICS) switch. Thus, in iron-replete cells, IRP1 assembles a cubane [4Fe-4S] cluster that prevents RNA-binding activity and renders the protein to cytosolic aconitase. We show that wild type or mutant forms of IRP1 that fail to assemble a [4Fe-4S] cluster are sensitized for iron-dependent degradation by the ubiquitin-proteasome pathway. The regulation of IRP1 abundance poses an alternative mechanism to prevent accumulation of inappropriately high IRE-binding activity when the ICS assembly pathway is impaired. To study functional aspects of IRP1, we overexpressed wild type or mutant forms of the protein in human H1299 lung cancer cells in a tetracycline-inducible fashion, and analyzed how this affects cell growth. While the induction of IRP1 did not affect cell proliferation in culture, it dramatically reduced the capacity of the cells to form solid tumor xenografts in nude mice. These data provide a first link between IRP1 and cancer.
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 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 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".