The Molecular Circadian Clock Is a Target ...
Type de document :
Compte-rendu et recension critique d'ouvrage
PMID :
Titre :
The Molecular Circadian Clock Is a Target of Anti-cancer Translation Inhibitors
Auteur(s) :
Berthier, Alexandre [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Gheeraert, Céline [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Johanns, Manuel [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Vinod, Manjula [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Eeckhoute, Jérôme [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Lefebvre, Philippe [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Gheeraert, Céline [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Johanns, Manuel [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Vinod, Manjula [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Eeckhoute, Jérôme [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Lefebvre, Philippe [Auteur]
![refId](/themes/Mirage2//images/idref.png)
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011 [RNMCD]
Titre de la revue :
Journal of Biological Rhythms
Éditeur :
SAGE Publications
Date de publication :
2023-10-23
ISSN :
0748-7304
Mot(s)-clé(s) en anglais :
Circadian REV-ERBα proteostasis anti-cancer drugs heart homoharringtonine
Circadian
REV-ERBα
proteostasis
anti-cancer drugs
heart
homoharringtonine
Circadian
REV-ERBα
proteostasis
anti-cancer drugs
heart
homoharringtonine
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely ...
Lire la suite >Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely regulated, thereby controlling the intrinsic cellular circadian clock. Genetic disruption of molecular clock components generally leads to marked pathological events phenotypically affecting behavior and multiple aspects of physiology. Using a transcriptional signature similarity approach, we identified anti-cancer protein synthesis inhibitors as potent modulators of the cardiomyocyte molecular clock. Eukaryotic protein translation inhibitors, ranging from translation initiation (rocaglates, 4-EGI1, etc.) to ribosomal elongation inhibitors (homoharringtonine, puromycin, etc.), were found to potently ablate protein abundance of REV-ERBα, a repressive nuclear receptor and component of the molecular clock. These inhibitory effects were observed both in vitro and in vivo and could be extended to PER2, another component of the molecular clock. Taken together, our observations suggest that the activity spectrum of protein synthesis inhibitors, whose clinical use is contemplated not only in cancers but also in viral infections, must be extended to circadian rhythm disruption, with potential beneficial or iatrogenic effects upon acute or prolonged administration.Lire moins >
Lire la suite >Circadian-paced biological processes are key to physiology and required for metabolic, immunologic, and cardiovascular homeostasis. Core circadian clock components are transcription factors whose half-life is precisely regulated, thereby controlling the intrinsic cellular circadian clock. Genetic disruption of molecular clock components generally leads to marked pathological events phenotypically affecting behavior and multiple aspects of physiology. Using a transcriptional signature similarity approach, we identified anti-cancer protein synthesis inhibitors as potent modulators of the cardiomyocyte molecular clock. Eukaryotic protein translation inhibitors, ranging from translation initiation (rocaglates, 4-EGI1, etc.) to ribosomal elongation inhibitors (homoharringtonine, puromycin, etc.), were found to potently ablate protein abundance of REV-ERBα, a repressive nuclear receptor and component of the molecular clock. These inhibitory effects were observed both in vitro and in vivo and could be extended to PER2, another component of the molecular clock. Taken together, our observations suggest that the activity spectrum of protein synthesis inhibitors, whose clinical use is contemplated not only in cancers but also in viral infections, must be extended to circadian rhythm disruption, with potential beneficial or iatrogenic effects upon acute or prolonged administration.Lire moins >
Langue :
Anglais
Vulgarisation :
Non
Projet ANR :
Source :
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