Fiche publication
Date publication
mai 2017
Journal
Cell death & disease
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BOIDOT Romain
,
Dr DUBREZ Laurence
,
Dr GARRIDO Carmen
,
Dr MICHEAU Olivier
Tous les auteurs :
Glorian V, Allègre J, Berthelet J, Dumetier B, Boutanquoi PM, Droin N, Kayaci C, Cartier J, Gemble S, Marcion G, Gonzalez D, Boidot R, Garrido C, Michaud O, Solary E, Dubrez L
Lien Pubmed
Résumé
The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control. Importantly, E2F1 stabilization in response to etoposide-induced DNA damage or during the S phase of cell cycle, as revealed by cyclin A silencing, is associated with K63-poly-ubiquitinylation of E2F1 on lysine 161/164 residues and involves cIAP1. Our results reveal an additional level of regulation of the stability and the activity of E2F1 by a non-degradative K63-poly-ubiquitination and uncover a novel function for the E3-ubiquitin ligase cIAP1.
Mots clés
Animals, Arginine, metabolism, DNA Damage, E2F1 Transcription Factor, metabolism, Humans, Inhibitor of Apoptosis Proteins, metabolism, Lysine, metabolism, Methylation, Mice, Polyubiquitin, metabolism, Protein Stability, S Phase, Structure-Activity Relationship, Transcription, Genetic, Ubiquitin-Protein Ligases, metabolism, Ubiquitination
Référence
Cell Death Dis. 2017 May;8(5):e2816
