The role of endogenous Bcl-xL in regulation of apoptotic signaling pathways.
Bibliographic record
Abstract
Bcl-2 proteins are major regulators of cellular responses to various apoptotic stimuli. Among them, overexpression of the anti-apoptotic BcI-2 protein BcI-xL modulates organelle-specific apoptotic pathways. To understand the mechanisms by which endogenous BcI-xL regulates apoptosis, mouse embryonic fibroblasts (MEFs) deficient in BcI-xL expression (Bcl-x-KO) was generated. Studies of BcI-xL exclusively targeted to an organelle in Bcl-x-KO MEFs indicate that the mitochondria- and ER-Iocalized BcI-xL play distinct roles in apoptosis resistance and Ca2+ homeostasis. Specifically, mitochondrial BcI-xL can regulate apoptosis independently of ER BcI-xL, and when localized exclusively at the ER, BcI-xL impinges on Ca2+ homeostasis but does not affect apoptosis unless BcI-xL is present in additional cellular compartments. Furthermore, I investigated how Bcl-2 proteins, especially Bcl-xL, might regulate oxidative stress-induced apoptosis. My studies reveal a signaling pathway, in which the oxidative stress inducer hydrogen peroxide (H202) activates Noxa, leading to a decrease in Mcl-1 expression levels and subsequent increase in apoptosis in the absence of BcI-xL expression. Finally, I studied the exact roles of lysosomal membrane permeabilization in apoptosis cascade triggered by oxidative stress and how LMP is regulated by the complex Bcl-2 protein network. My studies elucidate a novel molecular mechanism that couples lysosomal membrane permeabilization with mitochondrial membrane permeabilization and ultimate cell death during oxidative stress-induced apoptosis.
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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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".