DETERMINING THE ROLE OF GALECTIN1/HOXA5 INTERACTION AND REGULATION IN GLIOBLASTOMA DEVELOPMENT
Bibliographic record
Abstract
Abstract LGALS1 is directly transcribed by STAT3, which promotes glioblastoma tumorigenesis via its interaction with HOXA5. However, the underling molecular mechanism of this interaction remains uninvestigated. In this study, we predicted the interacting mode between galectin1 and HOXA5 using a protein-protein docking method. Our analysis suggests that the interaction between Galectin1 monomer and the homeobox domain of HOXA5 impedes the interaction between the homeobox domain of HOXA5 and DNA. In contrast, the interaction of Galectin1 homodimer and the N-terminal region of HOXA5 facilitates or stabilizes the homeobox domain of HOXA5 to bind DNA. Based on this predicted binding mode, we hypothesized that HOXA5 transcriptional activity is regulated by phosphorylated HOXA5, which may impact the interaction by attenuating the binding of HOXA5 to negatively charged DNA. To validate this model, we generated a mutant Galectin1 that cannot form dimers by substituting Cys at position 2 with Ser and Val at position 5 with Asp. We also generated functional domain deletion mutants of HOXA5 to confirm the interaction of the N- terminal region of HOXA5 with Galectin1, according to the prediction on functional domains in HOXA5 by Pfam. Using wild type (dimer) and mutant (monomer) recombinant galectin1 proteins and deletion-mutant proteins of HOXA5, we are conducting a binding assay to validate this model. Next, we employed knock-in lines to explore the role of HOXA5 phosphorylation in tumorigenesis using a glioblastoma mouse model. The proposed models will help uncover the underlying regulatory mechanisms of HOXA5/Galectin1 on BTSC self-renewal and glioblastoma tumorigenesis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".