A splice variant of cyclin D2 regulates cardiomyocyte cell cycle through a novel protein aggregation pathway
Bibliographic record
Abstract
The mammalian heart lacks intrinsic ability to replace diseased myocardium with newly divided myocytes. There is scant information on mechanisms regulating cell cycle exit in cardiomyocytes. We cloned a splice variant of cyclin D2 (D2SV) from the mouse heart and found a novel role for this protein in cardiomyocyte cell cycle exit. We report that D2SV is highly expressed in embryonic myocardium compared with the adult heart. Localization studies indicate that D2SV is retained in the endoplasmic reticulum (ER), Golgi and lysosomal compartments and subjected to ER-stress-associated protein aggregation. D2SV aggregation relies on the motor activities of dynein and is blocked by ER stress modulators. The ability of D2SV to sequester other cell cycle proteins provides a mechanistic explanation for its effects on cardiomyocyte cell cycle. We show that D2SV-induced cell cycle exit can be rescued by overexpression of D-type and B-type cyclins. We suggest that protein aggregation may be a major block for cardiomyocyte cell cycle reactivation.
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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".