ALTERNATIVELY SPLICED BNIP3 ISOFORM PROMOTES CELL SURVIVAL BY RECRUITING BCL‐2 TO THE IP3‐RECEPTOR
Bibliographic record
Abstract
Alternative splicing provides a versatile mechanism by which cells generate proteins with different or even antagonistic properties. We previously identified a novel splice variant of Bnip3 (Bnip3ΔEx3) generated in cardiac myocytes subjected to hypoxia. Like Full‐length Bnip3 (Bnip3FL), Bnip3ΔEx3 forms a complex with the antiapoptotic protein Bcl‐2; whereas, functional analysis of a Bnip3 mutant that lacks a Bcl‐2 interacting domain acts as a more potent inducer of programmed cell death, that can not be inhibited by Bnip3ΔEx3. In silico analysis of Bnip3ΔEx3 reveals an endoplasmic reticulum (ER) targeting domain within its C‐terminus, that is not present in Bnip3FL. We validated that Bnip3ΔEx3 is indeed localized to the ER and demonstrate that Bnip3ΔEx3 mutants that lack this ER targeting domain fail to antagonize cell death induced by Bnip3FL or hypoxia. Furthermore, we demonstrate that Bnip3ΔEx3 physically interacts with the IP3 receptor and serves to recruit Bcl‐2 to the ER; whereas, Bnip3ΔEx3 fails to protect against programmed cell death in the presence of a Bcl‐2 mutant that lacks its IP3 receptor interacting domain. Given the otherwise lethal consequences of de‐regulated Bnip3FL expression in post‐mitotic cells, our findings reveal a novel intrinsic defense mechanism that opposes the lethal consequences mitochondrial‐ER cross‐talk associated with programmed cell death in ventricular myocytes.
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 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".