Nesprin-2 contains BH3-like motifs that can promote cell death
Bibliographic record
Abstract
BH3-only proteins are a subgroup of the pro-apoptotic Bcl-2 family proteins. They initiate apoptosis by interacting with the multidomain pro- and anti-apoptotic Bcl-2 family proteins. SYNE2 encodes multiple nesprin-2 (Nes2) isoforms of which the most abundant and the largest is the nuclear envelope protein nesprin-2 giant (Nes2G). Nes2G is a component of the nuclear envelope Linker of Nucleoskeleton and Cytoskeleton (LINC) complex that connects the nucleus and the cytoskeleton. Previously, we showed that Nes2 has pro-apoptotic activity. We now show that Nes2G can bind multidomain pro-apoptotic and anti-apoptotic Bcl-2 family proteins and contains two BH3-like motifs near its N- and C-termini. Molecular modeling predicts that these BH3-like motifs have amphipathic α-helix structures and can dock onto the canonical groove of Bax and anti-apoptotic proteins as well as the trigger site of Bax. A chimeric tBid with its BH3 domain replaced with the C-terminal Nes2 BH3-like domain binds to Bax in cells. Furthermore, Nes2 BH3-like motif-containing fragments from the N- and the C-termini bind both pro-apoptotic and anti-apoptotic Bcl-2 proteins and promote cytochrome c release (indicative of apoptosis). Our results suggest that Nes2 acts as a BH3-only protein that regulates apoptosis by binding to the multidomain Bcl-2 family proteins.
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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) | 0.003 | 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".