Abstract A11: Biophysical characterization of the b-HLH-LZ of deltaMax
Bibliographic record
Abstract
Abstract Myc proteins (N-, L- and c-Myc) are transcriptional regulators with a broad spectrum of target genes. While essential for development, cell growth and proliferation as well as apoptosis, they play a major role in cancer onset and progression when deregulated. Myc protein functions depend on their heterodimerization with Max, another transcriptional regulator capable of forming a homodimer and antagonizing c-Myc transcriptional regulation. Recent studies have shown that c-Myc can control the alternative splicing of Max's pre-messenger RNA to produce a c-terminal truncated isoform called deltaMax. The ratio of deltaMax/WT-Max (p21) in cancer cells correlates with increased malignancy. In addition to producing a shorter gene product, the alternative splicing (exon-inclusion) generates a change in sequence in the LZ. The LZ domain is an integral and crucial part of the b-HLH-LZ motif of Max controlling its homodimerization and specific heterodimerization with c-Myc as well as binding to the E-box sequences found in gene promoters and enhancers. Whereas it has been demonstrated that deltaMax increases c-Myc transcriptional activities, the underlying mechanisms have not been elucidated yet. Here, we provide original insights into such mechanisms. First, we show that contrary to the WT motif, the b-HLH-LZ of deltaMax does not homodimerize. In addition, while the b-HLH-LZ of deltaMax can still heterodimerize with the b-HLH-LZ of c-Myc, it can no longer compete with the binding of the heterodimer to E-box sequences. Taken together, our results demonstrate that deltaMax can maximize the amount of c-Myc bound target gene promoters and enhancers and explain how deltaMax and the ratio of deltaMax/WT-Max (p21) in cancer cells can increase c-Myc oncogenic activities. Citation Format: Loïka Maltais, Cynthia Tremblay, Mikaël Bédard, Martin Montagne, Pierre Lavigne. Biophysical characterization of the b-HLH-LZ of deltaMax. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr A11.
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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".