Regulation of Bim in Health and Disease

Oncotarget. 2015 Sep 15;6(27):23058-134. doi: 10.18632/oncotarget.5492.


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.

Publication types

  • Review

MeSH terms

  • 3' Untranslated Regions
  • Alternative Splicing
  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Autoimmunity
  • Autophagy
  • Bcl-2-Like Protein 11
  • Cell Differentiation
  • Cytoskeleton / metabolism
  • Epigenesis, Genetic
  • Gene Expression Regulation*
  • Granulocytes / cytology
  • Humans
  • Immune System
  • Intercellular Signaling Peptides and Proteins
  • Killer Cells, Natural / cytology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / metabolism
  • Phosphorylation
  • Polymorphism, Genetic
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Transcription Factors / metabolism
  • Up-Regulation


  • 3' Untranslated Regions
  • Apoptosis Regulatory Proteins
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • MCL1 protein, human
  • Membrane Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins
  • Transcription Factors