Titre :

CDK8 Fine-Tunes IL-6 Transcriptional Activities by Limiting STAT3 Resident Time at the Gene Loci

Auteur(s) :

Martinez-Fabregas, Jonathan [Auteur]
University of Dundee
Wang, Luopin [Auteur]
Purdue University [West Lafayette]
Pohler, Elizabeth [Auteur]
University of Dundee
Cozzani, Adeline [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Institut pour la recherche sur le cancer de Lille [Lille] [IRCL]
Wilmes, Stephan [Auteur]
University of Dundee
Kazemian, Majid [Auteur correspondant]
Purdue University [West Lafayette]
Mitra, Suman [Auteur correspondant]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Institut pour la recherche sur le cancer de Lille [Lille] [IRCL]
Moraga, Ignacio [Auteur correspondant]
University of Dundee

Titre de la revue :

Cell Reports

Pagination :

108545 -

Éditeur :

Elsevier Inc

Date de publication :

2020-12-22

ISSN :

2211-1247

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Cytokines are highly pleiotropic ligands that regulate the immune response. Here, using interleukin-6 (IL-6) as a model system, we perform detailed phosphoproteomic and transcriptomic studies in human CD4+ T helper 1 (Th-1) ...
Lire la suite >Cytokines are highly pleiotropic ligands that regulate the immune response. Here, using interleukin-6 (IL-6) as a model system, we perform detailed phosphoproteomic and transcriptomic studies in human CD4+ T helper 1 (Th-1) cells to address the molecular bases defining cytokine functional pleiotropy. We identify CDK8 as a negative regulator of STAT3 transcriptional activities, which interacts with STAT3 upon IL-6 stimulation. Inhibition of CDK8 activity, using specific small molecule inhibitors, reduces the IL-6-induced phosphoproteome by 23% in Th-1 cells, including STAT3 S727 phosphorylation. STAT3 binding to target DNA sites in the genome is increased upon CDK8 inhibition, which results in a concomitant increase in STAT3-mediated transcriptional activity. Importantly, inhibition of CDK8 activity under Th-17 polarizing conditions results in an enhancement of Th-17 differentiation. Our results support a model where CDK8 regulates STAT3 transcriptional processivity by modulation of its gene loci resident time, critically contributing to diversification of IL-6 responses.Lire moins >

Langue :

Anglais

Vulgarisation :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL

Date de dépôt :

2024-02-17T03:39:23Z