Activation and Regulation of Interferon Regulatory Factor 4 in HTLV Type 1-Infected T Lymphocytes
Bibliographic record
Abstract
The human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL), an aggressive and fatal leukemia of CD4(+) T lymphocytes, and is also associated with a neurological demyelinating disease, tropical spastic paraparesis. The oncogenic potential of HTLV-1 resides in the 353-aa, 40-kDa viral Tax oncoprotein, a positive regulator of viral gene transcription. A novel member of the interferon regulatory factor (IRF) family of transcription factors, IRF-4, was shown to be constitutively produced in HTLV-1-infected cells. IRF-4 is transiently expressed in anti-CD3 and PMA/ionomycin-stimulated T lymphocytes but not in continuous non-Tax-expressing T cell lines. In transient coexpression assays, HTLV-1 Tax protein induced the 1. 2-kb IRF-4 promoter, indicating that Tax functions as an indirect trans-activator of the IRF-4 gene. Furthermore, IRF-4 levels in HTLV-1-infected cells appear to be proportional to the level of Tax expression, suggesting a role for IRF-4 in T cell transformation. In an effort to further characterize IRF-4 function, we identified a novel interaction between IRF-4 and FKBP52, a 59-kDa member of the immunophilin family with peptidyl-prolyl isomerase activity (PPIase). IRF-4-FKBP52 association inhibited the interaction between IRF-4 and its DNA-binding partner PU.1, as well as the trans-activation function of IRF-4/PU.1. FKBP52 association resulted in a structural modification of IRF-4, detectable by immunoblot analysis and by IRF-4 partial proteolysis. These results demonstrate a novel posttranslational mechanism of transcriptional control, mediated through the interaction of an immunophilin with a transcriptional regulator.
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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 | 0.000 |
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".