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Regulation of Bim in Health and Disease

2015; Impact Journals LLC; Volume: 6; Issue: 27 Linguagem: Inglês

10.18632/oncotarget.5492

1949-2553

Ronit Vogt Sionov, Spiros Vlahopoulos, Zvi Granot,

Autophagy in Disease and Therapy

// Ronit Vogt Sionov 1 , Spiros A. 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 : July 28, 2015 Accepted : August 08, 2015 Published : September 05, 2015 Abstract The BH3-only Bim protein is a major determinant for initiating the intrinsic apoptotic pathway under both physiological and pathophysiological conditions. Tight regulation of its expression and activity at the transcriptional, translational and post-translational levels together with the induction of alternatively spliced isoforms with different pro-apoptotic potential, ensure timely activation of Bim. 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. Enhanced Bim induction in neurons causes neurodegenerative disorders including Alzheimer’s, Parkinson’s and Huntington’s diseases. Moreover, type I diabetes is promoted by genetically predisposed elevation of Bim in β-cells. On the contrary, cancer cells have developed mechanisms that suppress Bim expression necessary for tumor progression and metastasis. This review focuses on the intricate network regulating Bim activity and its involvement in physiological and pathophysiological processes.