Document Detail

Apoptosis and autophagy: BIM as a mediator of tumour cell death in response to oncogene-targeted therapeutics.
MedLine Citation:
PMID:  19788418     Owner:  NLM     Status:  MEDLINE    
The BCL-2 homology domain 3 (BH3)-only protein, B-cell lymphoma 2 interacting mediator of cell death (BIM) is a potent pro-apoptotic protein belonging to the B-cell lymphoma 2 protein family. In recent years, advances in basic biology have provided a clearer picture of how BIM kills cells and how BIM expression and activity are repressed by growth factor signalling pathways, especially the extracellular signal-regulated kinase 1/2 and protein kinase B pathways. In tumour cells these oncogene-regulated pathways are used to counter the effects of BIM, thereby promoting tumour cell survival. In parallel, a new generation of targeted therapeutics has been developed, which show remarkable specificity and efficacy in tumour cells that are addicted to particular oncogenes. It is now apparent that the expression and activation of BIM is a common response to these new therapeutics. Indeed, BIM has emerged from this marriage of basic and applied biology as an important mediator of tumour cell death in response to such drugs. The induction of BIM alone may not be sufficient for significant tumour cell death, as BIM is more likely to act in concert with other BH3-only proteins, or other death pathways, when new targeted therapeutics are used in combination with traditional chemotherapy agents. Here we discuss recent advances in understanding BIM regulation and review the role of BIM as a mediator of tumour cell death in response to novel oncogene-targeted therapeutics.
Annette S Gillings; Kathryn Balmanno; Ceri M Wiggins; Mark Johnson; Simon J Cook
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2009-09-29
Journal Detail:
Title:  The FEBS journal     Volume:  276     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-14     Completed Date:  2009-10-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  6050-62     Citation Subset:  IM    
Laboratory of Molecular Signalling, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
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MeSH Terms
Apoptosis Regulatory Proteins / physiology*
Carcinoma, Non-Small-Cell Lung / drug therapy,  genetics
Cell Survival
Extracellular Signal-Regulated MAP Kinases / metabolism
Fusion Proteins, bcr-abl / antagonists & inhibitors
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
Membrane Proteins / physiology*
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
Neoplasms / drug therapy*,  pathology
Protein Processing, Post-Translational
Proto-Oncogene Proteins / physiology*
Proto-Oncogene Proteins B-raf / genetics
Receptor, Epidermal Growth Factor / genetics
Signal Transduction
Grant Support
//Biotechnology and Biological Sciences Research Council
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/Fusion Proteins, bcr-abl; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; EC, Epidermal Growth Factor; EC Proteins B-raf; EC Signal-Regulated MAP Kinases; EC Protein Kinase Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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