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

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.