IKKβ Is Required for Bcl-2-mediated NF-κB Activation in Ventricular Myocytes
Bibliographic record
Abstract
The transcription factor nuclear factor kappa B (NF-kappa B) is regulated by cytoplasmic inhibitor I kappa B alpha. An integral step in the activation of NF-kappa B involves the phosphorylation and degradation of I kappa B alpha. We have previously reported that I kappa B alpha activity is diminished in ventricular myocytes expressing Bcl-2 (de Moissac, D., Zheng, H., and Kirshenbaum, L. A. (1999) J. Biol. Chem. 274, 29505-29509). The underlying mechanism by which Bcl-2 activates NF-kappa B is undefined. In view of growing evidence that the I kappa B kinases (IKKs), notably IKK beta, are involved in signal induced phosphorylation of I kappa B alpha, we ascertained whether IKK beta is necessary and sufficient for Bcl-2 mediated NF-kappa B activation. Here we demonstrate that expression of Bcl-2 in ventricular myocytes resulted in an increase in NF-kappa B-dependent DNA binding, NF-kappa B gene transcription and reduced I kappa B alpha levels. An increase in the IKK beta kinase activity was observed in cells expressing full-length Bcl-2 but not in cells expressing the BH4 deletion mutant of Bcl-2 (Delta BH4; residues 10-30). Catalytically inactive mutants of IKK beta, but not IKK alpha, suppressed Bcl-2-mediated I kappa B alpha phosphorylation and NF-kappa B activation. Transfection of human embryonic 293 cells with a kinase-defective Raf-1 or a kinase-defective mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-1 (MEKK-1) suppressed Bcl-2-mediated IKK beta activity and NF-kappa B activation. Further, Bcl-2-mediated NF-kappa B activity was impaired in nullizygous mouse embryonic fibroblasts deficient for IKK beta. In this report, we provide the first direct evidence that Bcl-2 activates NF-kappa B by a signaling mechanism that involves Raf-1/MEKK-1 mediated activation of IKK beta.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".