Titre :

The Mediator complex subunit MED25 is targeted by the N-terminal transactivation domain of the PEA3 group members

Auteur(s) :

Verger, Alexis [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Mécanismes de la Tumorigénèse et Thérapies Ciblées - UMR 8161 [M3T]
baert, jean-luc [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF]
Verreman, Kathye [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Dewitte, Frederique [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Ferreira, Elisabeth [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Lens, Zoe [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
De Launoit, Yvan [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Villeret, Vincent [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]
Monte, Didier [Auteur]
Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] [IRI]

Titre de la revue :

Nucleic acids research

Nom court de la revue :

Nucleic Acids Res.

Numéro :

41

Pagination :

4847-4859

Date de publication :

2013-05

ISSN :

1362-4962

Mot(s)-clé(s) en anglais :

Cell Line
Humans
Transcriptional Activation
Transcription Factors
Protein Interaction Domains and Motifs
Mutation
Mediator Complex
DNA-Binding Proteins

Discipline(s) HAL :

Chimie/Chimie théorique et/ou physique

Résumé en anglais : [en]

PEA3, ERM and ER81 belong to the PEA3 subfamily of Ets transcription factors and play important roles in a number of tissue-specific processes. Transcriptional activation by PEA3 subfamily factors requires their characteristic ...
Lire la suite >PEA3, ERM and ER81 belong to the PEA3 subfamily of Ets transcription factors and play important roles in a number of tissue-specific processes. Transcriptional activation by PEA3 subfamily factors requires their characteristic amino-terminal acidic transactivation domain (TAD). However, the cellular targets of this domain remain largely unknown. Using ERM as a prototype, we show that the minimal N-terminal TAD activates transcription by contacting the activator interacting domain (ACID)/Prostate tumor overexpressed protein 1 (PTOV) domain of the Mediator complex subunit MED25. We further show that depletion of MED25 disrupts the association of ERM with the Mediator in vitro. Small interfering RNA-mediated knockdown of MED25 as well as the overexpression of MED25-ACID and MED25-VWA domains efficiently inhibit the transcriptional activity of ERM. Moreover, mutations of amino acid residues that prevent binding of MED25 to ERM strongly reduce transactivation by ERM. Finally we show that siRNA depletion of MED25 diminishes PEA3-driven expression of MMP-1 and Mediator recruitment. In conclusion, this study identifies the PEA3 group members as the first human transcriptional factors that interact with the MED25 ACID/PTOV domain and establishes MED25 as a crucial transducer of their transactivation potential.Lire moins >

Langue :

Anglais

Audience :

Non spécifiée

Établissement(s) :

CNRS
Université de Lille

Collections :

• Mécanismes de la Tumorigénèse et Thérapies Ciblées (M3T) - UMR 8161
• Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576

Équipe(s) de recherche :

Biologie structurale et intégrative

Date de dépôt :

2020-02-12T15:11:32Z
2021-03-26T07:30:13Z