BCL‐2‐family protein tBID can act as a BAX‐like effector of apoptosis

• DOI: 10.15252/embj.2021108690
• Publication Date: 2021-12-21T11:00:33Z
• Authors: Hector Flores‐Romero; Lisa Hohorst; Malina John; Marie‐Christine A...; Louise E King; Laura Beckmann; Tamas Szabo; Vanessa Hertlein; Xu Luo; Andreas Villunger; Lukas P Frenzel; Hamid Kashkar; Ana J Garcia‐Saez
• Keywords: Bcl-2 Family; Bcl-2-associated X protein

During apoptosis, the BCL-2-family protein tBID promotes mitochondrial permeabilization by activating BAX and BAK blocking anti-apoptotic BCL-2 members. Here, we report that can also mediate itself, resulting in release of cytochrome c DNA, caspase activation apoptosis even absence BAK. This previously unrecognized activity depends on helix 6, homologous to pore-forming regions BAK, be blocked pro-survival proteins. Importantly, tBID-mediated independent is physiologically relevant for SMAC immune response against Shigella infection. Furthermore, it exploited kill leukaemia cells with acquired venetoclax resistance due lack active Our findings define as an effector provide a new paradigm proteins, implications anti-bacterial immunity cancer therapy.