title: Regulation of Bim in Health and Disease.
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.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ronit Vogt
authors.initials: RV
authors.lastname: Sionov
authors.affiliation: First Department of Pediatrics, University of Athens, Horemeio Research Laboratory, Thivon and Levadias, Goudi, Athens, Greece.
authors.forename: Spiros A
authors.initials: SA
authors.lastname: Vlahopoulos
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Granot
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015551:Autoimmunity; D001343:Autophagy; D000072224:Bcl-2-Like Protein 11; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000378:metabolism; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D007107:Immune System; D036341:Intercellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C579095:MCL1 protein, human; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors
keywords: Bim; apoptosis; autoimmunity; cancer; neurodegenerative diseases