Abstract A39: Sall2 tumor suppressor protein is a novel Casein Kinase 2 target
Bibliographic record
Abstract
Abstract Sall2 is a transcription factor with critical roles during development, including neurogenesis and eye formation. Importantly, Sall2 has also been associated with cancer, although its contribution to the disease remains controversial. Sall2 is down-regulated in several tumor types and its activity promotes cell cycle arrest and cell death. Despite its role as a tumor suppressor, little is known about its regulation. In order to identify regulatory mechanisms of Sall2 protein, bioinformatic analysis were performed. Preliminary data lead to the identification of several putative phosphorylation sites within a potential and highly conserved PEST motif. All of these sites match the consensus sequence for Casein Kinase 2 (CK2)-mediated phosphorylation. CK2 is a ubiquitous and constitutively active kinase whose activity is increased in cancer cells. CK2 promotes both cell survival and proliferation by regulating stability, activity and/or subcellular localization of its target proteins, including tumor suppressors. With the aim of determining whether Sall2 is regulated by CK2, several approaches such as pharmacological inhibition of CK2, mass spectrometry analysis, immunofluorescence, immunoprecipitation, in vitro kinase assays and site directed mutagenesis were used. Our results indicate that Sall2 is a CK2 target in vitro. In cells, CK2 interacts with Sall2 and triggers the ubiquitination and subsequent degradation of Sall2 in a proteasome-mediated fashion. Moreover, phosphorylation of Sall2 at S763 and T778 was greatly reduced under CK2 inhibition, suggesting that these are the most important CK2-dependent phospho-sites in vivo. In conclusion, we have identified Sall2 as a new CK2 target. Our results support a novel regulatory mechanism for Sall2 degradation and provide new insights into the means by which CK2 promotes cell survival and proliferation, two characteristic requirements of cancer cells. FUNDING: FONDECYT1151031, CIHR Citation Format: Viviana Hermosilla, Adam Rabalski, Laszlo Gyenis, David W. Litchfield, Roxana Pincheira. Sall2 tumor suppressor protein is a novel Casein Kinase 2 target. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr A39.
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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) | 0.004 | 0.002 |
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".