Aberrant activation of STAT3 in primary human endothelial cells by the latent KSHV protein kaposin B (39.18)
Bibliographic record
Abstract
Abstract The proto-oncogene STAT3 is a latent transcription factor that upon activation drives the expression of a number of genes involved in cell proliferation, survival, and immune responses. Canonical STAT3 activation occurs via phosphorylation of Y705, dimerization, and nuclear translocation, followed by phosphorylation of S727 for maximal transcriptional activity. Kaposi’s sarcoma associated herpesvirus (KSHV) is the infectious cause of several AIDS-related cancers including Kaposi’s sarcoma (KS). Here we show that latent KSHV infection of primary human endothelial cells (ECs) activates STAT3, and identify a key latency protein, kaposin B, that contributes to this activation. Kaposin B expression in ECs causes STAT3 phosphorylation at S727, relocalization to punctate structures within the nucleus known as ‘STAT3 bodies’, and enhanced expression of STAT3 target genes. Recent work shows that the tripartite motif-containing protein 28 (TRIM28, a.k.a. TIF-1β, KAP-1) negatively regulates STAT3 by recruiting transcriptional silencing complexes. Here, we demonstrate for the first time that TRIM28 is a bona fide target of the host cell kinase MK2 and show that KSHV infection and kaposin B expression results in MK2 activation and concomitant phosphorylation and inactivation of TRIM28. Taken together, our studies reveal an important new regulatory mechanism governing STAT3 activation in endothelial cells and suggest novel protein targets for the treatment of KS.
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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) | 0.002 | 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".