Transcriptional regulation of human <scp>USP</scp>24 gene expression by NF‐kappa B
Bibliographic record
Abstract
Abstract Impairment of the ubiquitin proteasome pathway is believed to play an important role in the pathogenesis of Parkinson's disease. This process is carried out under tight regulation by deubiquitinating enzymes. Genetic linkage studies indicated that the region of the human ubiquitin‐specific protease 24 (USP24) gene is significantly correlated with Parkinson's disease. In this study, we cloned a 1648 bp 5′ flanking region of the human USP24 gene coding sequence and a series of nested deletions into the pGL3‐Basic vector. We analyzed promoter activities of these regions with a luciferase‐based reporter assay system. A 64‐bp region was identified to contain the transcription initiation site and a minimum promoter sequence for transcriptional activation of the USP24 gene expression. Expression of USP24 is controlled by a TATA‐box‐less promoter with several putative cis‐acting elements. Transcriptional activation and gel‐shift assay demonstrated that the USP24 gene promoter contains a functional NFκB‐binding site. Over‐expression of nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NFκB) and tumor‐necrosis factor alpha (TNFα) treatment significantly increased the USP24 promoter activity, mRNA expression and protein level in human HEK293 cells, mouse N2a cells and human neuroblastoma SH‐SY5Y cells. Deletion and mutation of the binding site abolished the regulatory effect of NFκB on human USP24 gene transcription. These results suggested that USP24 expression is tightly regulated at its transcription level and NFκB plays an important role in this process. image Impairment of the ubiquitin proteasome system (UPS) has been implicated in neurodegenerative disorders. This report showed that the expression of human ubiquitin‐specific protease 24 (USP24), a deubiquitinating enzyme of UPS, is tightly regulated by NFκB. The results suggest that dysregulation of NFκB‐mediated USP24 expression may play a role in PD pathogenesis and modulating this process could have therapeutic potential.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".