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E2F1 interacts with BCL ‐ xL and regulates its subcellular localization dynamics to trigger cell death
Author(s) -
Vuillier Céline,
Lohard Steven,
Fétiveau Aurélie,
Allègre Jennifer,
Kayaci Cémile,
King Louise E,
Braun Frédérique,
BarilléNion Sophie,
Gautier Fabien,
Dubrez Laurence,
Gilmore Andrew P,
Juin Philippe P,
Maillet Laurent
Publication year - 2018
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744046
Subject(s) - microbiology and biotechnology , bcl xl , effector , e2f1 , programmed cell death , transcription factor , mitochondrion , apoptosis , regulator , suppressor , biology , chemistry , cell cycle , gene , biochemistry
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 BH 3 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‐ BH 3‐binding regulator of BCL ‐ xL localization dynamics that influences its anti‐apoptotic activity.