Characterization of Growth Suppressive Functions of a Splice Variant of Cyclin D2
Bibliographic record
Abstract
We have recently cloned a novel splice variant of cyclin D2 termed as cycD2SV. CycD2SV overexpression in several immortalized cell lines led to formation of ubiquitinated protein aggregates accompanied by a significant decrease in cell proliferation. Based on immuno co-localization and ultrastructural analysis experiments, cycD2SV protein aggregates were frequently found in various subcellular compartments such as endosomes, autophagosomes, lysosomes and the microtubule organizing centre. Secondary structure analysis revealed that the amino terminal α-helix in cycD2SV is not tightly packed with the cyclin box suggesting a misfolded conformation compared to other cyclins. Deletion analysis suggests that 1-53 amino acid region of cycD2SV may be required for protein aggregation and 54-136 amino acid region may mediate cell cycle inhibition. Based on co-immunoprecipitation experiments, we have shown that cycD2SV binds to cycD2 as well as CDK4. In addition, gene expression analysis demonstrated an upregulation in GADD45α and dynamin 2 mRNA levels in cycD2SV overexpressing cells. These two proteins are known to play critical roles in the DNA damage response and apoptosis pathways. TUNEL experiments were negative for apoptosis, however, cycD2SV expressing cells were more sensitive to cell death induced by external stressors such as trypsinization. Collectively our results suggest that cycD2SV mediates cell cycle inhibition by sequestering endogenous cell cycle proteins, such as cycD2 and CDK4, and possibly targeting them for ubiquitin mediated protein degradation.
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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".