Over the past decade, Bim has emerged as an essential pro-apoptotic protein for initiating the intrinsic apoptotic pathway under many physiological and pathophysiological conditions. While this is important, because an initiating step gets subsequently amplified, in many diseases a downstream step malfunctions, making most available drug treatments futile. It has become apparent that many pharmaceutical agents target only the initiating step in an intracellular signal cascade. This review focuses on the intricate network regulating Bim activity and its involvement in physiological and pathophysiological processes. Moreover, type I diabetes is promoted by genetically predisposed elevation of Bim in -cells. Under physiological conditions, Bim is essential for shaping immune responses where its absence promotes autoimmunity, while too early Bim induction eliminates cytotoxic T cells prematurely, resulting in chronic inflammation and tumor progression.Įnhanced Bim induction in neurons causes neurodegenerative disorders including Alzheimers, Parkinsons and Huntingtons diseases. Vlahopoulos 2 and Zvi Granot 1 1 Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University, Hadassah Medical School, Jerusalem, Israel 2 First Department of Pediatrics, University of Athens, Horemeio Research Laboratory, Thivon and Levadias, Goudi, Athens, Greece Correspondence to: Ronit Vogt Sionov, email: Keywords: Bim, apoptosis, cancer, autoimmunity, neurodegenerative diseases Received: JAccepted: AugPublished: SeptemAbstract The BH3-only Bim protein is a major determinant for initiating the intrinsic apoptotic pathway under both physiological and pathophysiological conditions.
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February 2023
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