T-cell protein tyrosine phosphatase (TC-PTP) regulates Stat3 signaling in mouse epidermis after UVB irradiation
Bibliographic record
Abstract
3920 Ultraviolet B radiation (UVB) can cause DNA damage, induce gene mutations and modulate intracellular signal transduction contributing to the development of skin cancer. Signal transducer and activator of transcription 3 (Stat3) modulates various physiological functions including apoptosis, cell cycle regulation, and tumor angiogenesis through regulation of gene expression, and its constitutive activation is associated with human epithelial cancers. Recent studies indicated that Stat3 was rapidly dephosphorylated in keratinocytes after UVB irradiation. Vanadate treatment desensitized keratinocytes to UVB-induced apoptosis with the recovery of phosphorylated Stat3 protein levels, implying that a tyrosine phosphatase is involved in this mechanism. In the current work, the mechanism whereby UVB exposure leads to rapid dephosphorylation of Stat3 was examined. Western blot analysis showed that the nuclear form of TC-PTP, which is known to dephosphorylate various signaling molecules, was constitutively expressed in cultured mouse keratinocytes. After UVB exposure, activated stat3 was rapidly reduced, whereas the level of TC-PTP was not changed. Further immunofluorescence and western blot analyses revealed that TC-PTP translocates from cytosol to nucleus in response to UVB irradiation. Dephosphorylation of Stat3 by TC-PTP was rapidly increased after UVB irradiation of cultured keratinocytes with nuclear accumulation of TC-PTP. Stat3 target genes, such as cyclin D1 and c-Myc, were also down-regulated early following UVB exposure. Consistent with these observations, RNAi studies showed that the level of phosphorylated Stat3 in keratinocytes transfected with TC-PTP siRNA was higher compared with control keratinoctyes upon UVB irradiation. In addition, Inhibition of importin β1 expression by siRNA knockdown of importin β1, which is known to transport TC-PTP in to the nucleus, did not prevent its translocation and dephosphorylatin of Stat3 in nucleus, indicating that UVB-induced transport of TC-PTP is independent of importin β1. In mouse epidermis in vivo, the level of phosphorylated Stat3 was initially decreased, following by a significant increase at later time points after UVB exposure. The expression patterns of cyclin D1 and c-Myc followed the changes in activated Stat3. Consistently, dephosphorylation of Stat3 by TC-PTP was initially increased, and then decreased in vivo after UVB exposure. These results suggest that TC-PTP is responsible for the rapid dephosphorylation of Stat3 following UVB and may serve as part of an initial protective mechanisms against UV skin carcinogenesis.
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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 | 0.001 |
| 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".