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

Autor: Flores-Romero H; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Interfaculty Institute of Biochemistry, Eberhard-Karls-Universität Tübingen, Tübingen, Germany., Hohorst L; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., John M; Interfaculty Institute of Biochemistry, Eberhard-Karls-Universität Tübingen, Tübingen, Germany., Albert MC; Institute for Molecular Immunology, and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany., King LE; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany., Beckmann L; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.; Center of Integrated Oncology ABCD, University Hospital of Cologne, Cologne, Germany., Szabo T; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria., Hertlein V; Interfaculty Institute of Biochemistry, Eberhard-Karls-Universität Tübingen, Tübingen, Germany., Luo X; Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, ME, USA.; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA., Villunger A; Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria., Frenzel LP; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany.; Center of Integrated Oncology ABCD, University Hospital of Cologne, Cologne, Germany., Kashkar H; Institute for Molecular Immunology, and Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany., Garcia-Saez AJ; Institute for Genetics, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.; Interfaculty Institute of Biochemistry, Eberhard-Karls-Universität Tübingen, Tübingen, Germany.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2022 Dec 17; Vol. 41 (2), pp. e108690. Date of Electronic Publication: 2021 Dec 21.
DOI: 10.15252/embj.2021108690
Abstrakt: During apoptosis, the BCL-2-family protein tBID promotes mitochondrial permeabilization by activating BAX and BAK and by blocking anti-apoptotic BCL-2 members. Here, we report that tBID can also mediate mitochondrial permeabilization by itself, resulting in release of cytochrome c and mitochondrial DNA, caspase activation and apoptosis even in absence of BAX and BAK. This previously unrecognized activity of tBID depends on helix 6, homologous to the pore-forming regions of BAX and BAK, and can be blocked by pro-survival BCL-2 proteins. Importantly, tBID-mediated mitochondrial permeabilization independent of BAX and BAK is physiologically relevant for SMAC release in the immune response against Shigella infection. Furthermore, it can be exploited to kill leukaemia cells with acquired venetoclax resistance due to lack of active BAX and BAK. Our findings define tBID as an effector of mitochondrial permeabilization in apoptosis and provide a new paradigm for BCL-2 proteins, with implications for anti-bacterial immunity and cancer therapy.
(© 2021 The Authors Published under the terms of the CC BY 4.0 license.)
Databáze: MEDLINE
Externí odkaz: