SUN-014 Identification of a New SUMOylation Process Regulating Nuclear Receptor Nor-1
Bibliographic record
Abstract
Nuclear receptors are transcriptional factors controlling critical gene expression networks essential to the developmental and homeostatic regulation of several physiological processes. Transcriptional control of nuclear receptors is achieved by interaction with specific ligands and in response to cellular signalling pathways, which often results in post-translational modifications of receptors. Among such modifications, SUMOylation has emerged as a key process regulating nuclear receptor function. Our recent work has revealed an atypical SUMOylation process that requires phosphorylation, thereby defining a novel SUMO conjugating motif termed pSuM. Functional pSuM has been described for estrogen nuclear receptor ERβ and bile acid receptor FXR, and sequence analysis has indicated a conserved pSuM in the orphan nuclear receptor Nor-1. This study aims to characterize the function of Nor-1 pSuM-mediated SUMOylation. Nor-1 has various functions in the nervous system, including a role in neuronal survival and hippocampal development. In line with an implication of the SUMOylation process in neurodegenerative diseases, we speculate that pSuM SUMOylation might regulate Nor-1 activity and participate in the maintenance of neuronal integrity. The SUMOylation potential of Nor-1 and the mechanism regulating this process were investigated using immunoprecipitation and Western blot analysis. Our results indicate that Nor-1 was SUMOylated at the pSuM motif as well as at another consensus SUMOylation motif, thereby conjugating SUMO-1 and SUMO-2. We also found that the phosphorylation of the pSuM motif was essential for pSuM activation and SUMO conjugation. Furthermore, phosphorylation of adjacent residues to the pSuM appeared to potentiate the SUMOylation of Nor-1, suggesting a role for pSuM extension. This demonstrates the implication of specific kinase pathways required to promote pSuM activation. Using luciferase reporter assays and qPCR analysis, we also showed that SUMOylation regulates Nor-1 transcriptional activity and responsive gene expression in neuronal cells. Our findings provide new insights on the mechanistic regulation of Nor-1 function by phosphorylation and SUMOylation. We also identify a new atypical and highly regulated SUMOylation process as an additional targeting possibility for SUMO conjugation to coordinate transcriptional competence. This study contributes to expand the intricate dynamics of the SUMOylation process used by incoming signals to govern gene networks by nuclear receptors and possibly other transcription factors. Sources of Research Support: This work is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC), Canadian Institute of Health Research (CIHR) award, and Fonds de la recherche en santé du Québec (FRQS) award.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".