Abstract 164: The Chaperone Holdase Bag6 Modulates the Intracellular Fate of Newly Synthesized ApoB100
Bibliographic record
Abstract
Apolipoprotein B-100 (apoB) is the central protein component of very low density lipoproteins (VLDL) and is subject to endoplasmic reticulum-associated degradation (ERAD). Hepatic assembly of VLDL particles is monitored by the cellular quality control machinery, which determines whether a properly formed lipoprotein is secreted or the inadequately lipidated apoB protein is degraded. Changes in lipid supply, ER folding capacity or ERAD pathway function can alter VLDL output from HepG2 cells. Bag6 is a cytosolic protein that has a role in the bilayer integration of proteins and is also implicated in maintaining the solubility of proteasome substrates that contain exposed hydrophobic regions. Notably, Bag6 has been observed to interact with the ERAD components gp78 and p97, which are known to facilitate apoB degradation. The goal of this study was to evaluate the role of cytosolic Bag6 in apoB metabolism in HepG2 cells. When MG132 was used to inhibit proteasomal degradation of apoB, Bag6 was co-immunoprecipitated with apoB as determined by functional proteomics and immunoblot analysis. Conversely, if VLDL assembly was enhanced by treatment of the cells with the MEK/ERK inhibitor U0126, both the Bag6-apoB and p97-apoB associations were no longer detectable. Metabolic labelling studies indicated that siRNA knockdown of Bag6 did not alter the initial rate of apoB biosynthesis, but decreased the secretion of newly synthesized apoB. The decrease in apoB secretion with Bag6 knockdown could not be reversed by U0126. In addition, Bag6 knockdown decreased the effectiveness of MG132 as an inhibitor of cellular apoB degradation even though ubiquitination of apoB appeared to be unaffected. These observations suggest that Bag6 may be a component of the ERAD pathway that modulates VLDL assembly. Reduction of Bag6 partially decreases both secretion and MG132-inhibitable degradation of apoB, suggesting that another mechanism is also involved in apoB degradation. We hypothesize that the “holdase” function of Bag6 may temporarily stabilize exposed hydrophobic domains of apoB prior to its progression to assembly or 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".