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Oncotarget. 2015 Sep 15;6(27):23058-134.

Regulation of Bim in Health and Disease.

Author information

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.

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.

KEYWORDS:

Bim; apoptosis; autoimmunity; cancer; neurodegenerative diseases

PMID:
26405162
PMCID:
PMC4695108
DOI:
10.18632/oncotarget.5492
[Indexed for MEDLINE]
Free PMC Article

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