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EMBO Rep. 2018 Feb;19(2):234-243. doi: 10.15252/embr.201744046. Epub 2017 Dec 12.

E2F1 interacts with BCL-xL and regulates its subcellular localization dynamics to trigger cell death.

Author information

1
CRCINA, INSERM, U1232, Université de Nantes, Nantes, France.
2
LNC, INSERM, UMR866, Université de Bourgogne Franche-Comté, Dijon, France.
3
Wellcome Centre for Cell-Matrix Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.
4
ICO René Gauducheau, Saint Herblain, France.
5
CRCINA, INSERM, U1232, Université de Nantes, Nantes, France philippe.juin@univ-nantes.fr laurent.maillet@univ-nantes.fr.

Abstract

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.

KEYWORDS:

BCL‐2 family; BCL‐xL mobility; E2F1; apoptosis

PMID:
29233828
PMCID:
PMC5797968
[Available on 2019-02-01]
DOI:
10.15252/embr.201744046
[Indexed for MEDLINE]

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