The role of insulin‐like growth factor binding protein‐6 in mediating cell fate
Bibliographic record
Abstract
The insulin‐like growth factor (IGF) family is composed of IGF‐I and II, type I and II receptors, binding proteins, and binding protein related proteins. These proteins are involved in regulating normal cell growth and development, promoting proliferation, survival and differentiation, and exerting metabolic actions. Six IGF specific binding proteins, IGFBP‐1 to ‐6, have been characterized. These proteins are modulators of IGF activity and have IGF‐independent actions. IGFBP‐6 is a ubiquitous protein that binds IGF‐II with high affinity. It has a predicted nuclear localization signal (NLS) and casein kinase II binding site (CKII‐BS). IGFBP‐6 has diverse roles in various cell types; including inhibiting cell proliferation, inducing apoptosis, and reducing tumorigenicity. The rhabdomyosarcoma derived (RD) cell line is a muscle tumor cell line capable of myogenesis that expresses IGFBP‐6 at high levels. TAP‐tagged IGFBP‐6 wildtype (wt) and mutant clones were created to explore protein‐protein interactions of IGFBP‐6, and elucidate the role of IGFBP‐6 and its signaling partners in mediating cell fate. IGFBP‐6 was found to bind 14‐3‐3 an anti‐apoptotic factor, nuclear proteins such as importin and muscle proteins such as α‐actinin. Overexpression of wt‐IGFBP‐6 induces apoptosis in RD cells, but mutations in the CKII‐BS and the NLS reduce the effect. Initial results suggest IGFBP‐6 plays a role in preventing myogenic conversion in RD cells, and mutations in the CKII‐BS appear to overcome this inhibition. Taken together these early results suggest that IGFBP‐6 may play a key role in determining whether cells enter the apoptotic or myogenic pathway. This work was supported by CIHR
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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 | 0.001 |
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".