Immunoproteasomes regulate gene expression in dendritic cells (100.36)
Bibliographic record
Abstract
Abstract A constitutive form of the proteasome (CP) is expressed in all eukaryotic cells and is involved in many cellular processes. Immune and cytokine-activated cells also express a second type of proteasome named the immunoproteasome (IP). Since its discovery, it has been thought that the main role of IPs is to produce MHC I-associated peptides. However, an increasing number of studies report peptide-independent effects of IPs. In line with this, we recently showed using microarrays that knocking-out two IP-subunits (LMP7 and MECL1) in bone marrow-derived dendritic cells alters the expression of 171 genes mostly associated with immune functions, with enriched clusters on chromosomes. We now show by qPCR experiments that the disruption of both LMP7 and MECL1 is necessary to alter gene expression. Bioinformatic predictions of transcription factor binding sites suggest that this effect of IPs hinges mainly on transcriptional regulation. Comparing the abundance of unspliced and mature mRNAs in WT and IP knock-out cells shows that IPs also influence the maturation of certain transcripts. However, IPs do not affect mRNA stability overtime when blocking mRNA synthesis. The control of gene expression by IPs might explain aberrant T and B cell phenotypes previously described in IP-subunit knock-out mice. A better comprehension of how IPs regulate gene expression could help us understand the selective pressure that allowed the conservation of more than one type of proteasome in vertebrates.
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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 | 0.000 |
| 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".