Loss Of Calreticulin Function Decreases NFKB Activity By Stabilizing IKB Protein
Bibliographic record
Abstract
Abstract Background: Transcription factor NF K B is activated by several processes including inflammation, endoplasmic-reticulum (ER) stress, increased Akt signaling and enhanced proteasomal degradation. Calreticulin is an ER Ca 2+ binding chaperone, which regulates many cellular processes. Previously, we have shown that loss of calreticulin function results in the activation of ER stress that is accompanied by a significant increase in the proteasome activity. These changes increase the resistance of calreticulin deficient cells to apoptosis. A role for calreticulin has also been described in the regulation of immune response. Objectives: To examine the role of calreticulin in the activation of NF K B signaling leading to enhanced resistance to apoptosis of these cells. Methods:: Wild type and calreticulin deficient cells were used for measurement of transcriptional activity of NF K B. Cells were co-transfected with of NF K B reporter and-gal reporter plasmids followed by reporter gene assays. Western blot analysis was utilized to examine changes in protein expression. Results: Our data illustrate a significant decrease in the basal transcriptional activity of NF K B upon loss of calreticulin function. Furthermore, treatment with lipopolysaccharide increased the transcriptional activity of NF K B in both the wild type and calreticulin deficient cells. However, the transcriptional activity of NF K B was still significantly lower in the calreticulin deficient cells as compared to the wild type cells. Our data also showed that the reduced NF K B activity in calreticulin deficient cells is not due to decreased p65 or p50 protein levels. To determine the mechanism of decreased NF K B activity we examined changes in IKB protein stability. Our data showed a significant increase in the IKB protein level due to decreased level of phosphorylated IKB protein. Furthermore, we illustrated that loss of calreticulin function resulted in increased protein phosphatase2A activity that was abolished by Okadaic acid treatment. Inhibition of IKB de-phosphorylation decreased its ubiquitination and proteasomal degradation. Conclusion: Our data suggests that the reduced transcriptional activity of NF K B upon loss of calreticulin function is mediated via stabilization of IKB protein. To our knowledge, this is the first report on the role of calreticulin in the regulation of NF K B function.
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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 teacher head, 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".