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

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Vuillier, Céline | Lohard, Steven | Fétiveau, Aurélie | Allègre, Jennifer | Kayaci, Cémile | King, Louise, E | Braun, Frédérique | Barillé-Nion, Sophie | Gautier, Fabien, P | Dubrez, Laurence | Gilmore, Andrew, P | Juin, Philippe | Maillet, Laurent, A

Edité par CCSD ; EMBO Press -

International audience. 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.

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