SUN-014 Identification of a New SUMOylation Process Regulating Nuclear Receptor Nor-1
Notice bibliographique
Résumé
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.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».