دورية أكاديمية
CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium
| العنوان: | CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium |
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| المؤلفون: | Prieto, Susana, Dubra, Geronimo, Camasses, Alain, Aznar, Ana, Bella, Begon-Pescia, Christina, Simboeck, Elisabeth, Pirot, Nelly, Gerbe, François, Angevin, Lucie, Jay, Philippe, Krasinska, Liliana, Fisher, Daniel |
| المساهمون: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Ligue Nationale Contre le Cancer (LNCC), Institut régional de Cancérologie de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Réseau d'histologie expérimentale de Montpellier (RHEM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| المصدر: | ISSN: 1469-221X. |
| بيانات النشر: | HAL CCSD EMBO Press |
| سنة النشر: | 2023 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | CDK19, CDK8, CFTR, intestinal epithelium, Mediator, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; CDK8 and CDK19 form a conserved cyclin-dependent kinase subfamily that interacts with the essential transcription complex, Mediator, and also phosphorylates the C-terminal domain of RNA polymerase II. Cells lacking either CDK8 or CDK19 are viable and have limited transcriptional alterations, but whether the two kinases redundantly control cell proliferation and differentiation is unknown. Here, we find in mice that CDK8 is dispensable for regulation of gene expression, normal intestinal homeostasis, and efficient tumourigenesis, and is largely redundant with CDK19 in the control of gene expression. Their combined deletion in intestinal organoids reduces long-term proliferative capacity but is not lethal and allows differentiation. However, double-mutant organoids show mucus accumulation and increased secretion by goblet cells, as well as downregulation of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and functionality of the CFTR pathway. Pharmacological inhibition of CDK8/19 kinase activity in organoids and in mice recapitulates several of these phenotypes. Thus, the Mediator kinases are not essential for cell proliferation and differentiation in an adult tissue, but they cooperate to regulate specific transcriptional programmes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36545778; hal-03911208; https://hal.science/hal-03911208Test; https://hal.science/hal-03911208/documentTest; https://hal.science/hal-03911208/file/CDK8%20and%20CDK19%20act%20redundantly%20to%20control%20the%20CFTR%20pathway%20in%20the%20intestinal%20epithelium%20Prieto%20EMBO%20Reports%202022.pdfTest; PUBMED: 36545778 |
| DOI: | 10.15252/embr.202154261 |
| الإتاحة: | https://doi.org/10.15252/embr.202154261Test https://hal.science/hal-03911208Test https://hal.science/hal-03911208/documentTest https://hal.science/hal-03911208/file/CDK8%20and%20CDK19%20act%20redundantly%20to%20control%20the%20CFTR%20pathway%20in%20the%20intestinal%20epithelium%20Prieto%20EMBO%20Reports%202022.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.DA10A190 |
| قاعدة البيانات: | BASE |
| DOI: | 10.15252/embr.202154261 |
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