E2F1 interacts with BCL-xL and regulates its subcellular localization dynamics to trigger cell death.
Fiche publication
Date publication
février 2018
Journal
EMBO reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr DUBREZ Laurence
Tous les auteurs :
Vuillier C, Lohard S, Fétiveau A, Allègre J, Kayaci C, King LE, Braun F, Barillé-Nion S, Gautier F, Dubrez L, Gilmore AP, Juin PP, Maillet L
Lien Pubmed
Résumé
E2F1 is the main pro-apoptotic effector of the pRB-regulated tumor suppressor pathway by promoting the transcription of various pro-apoptotic proteins. We report here that E2F1 partly localizes to mitochondria, where it favors mitochondrial outer membrane permeabilization. E2F1 interacts with BCL-xL independently from its BH3 binding interface and induces a stabilization of BCL-xL at mitochondrial membranes. This prevents efficient control of BCL-xL over its binding partners, in particular over BAK resulting in the induction of cell death. We thus identify a new, non-BH3-binding regulator of BCL-xL localization dynamics that influences its anti-apoptotic activity.
Mots clés
BCL‐2 family, BCL‐xL mobility, E2F1, apoptosis
Référence
EMBO Rep.. 2018 Feb;19(2):234-243