Abstract
The mechanism by which the cell death mediator Bax becomes activated to cause mitochondrial damage, a key step for the intrinsic pathway to apoptosis, remain highly contentious. Although some data support a role for certain BH3-only proteins, such as Bim or tBid, to directly activate Bax, others have led to the conclusion that BH3-only proteins act indirectly by antagonizing the prosurvival Bcl-2 proteins, thereby allowing Bax activation to proceed. A recent paper in Nature by Gavathiotis et al. provides the first biophysical evidence for a direct interaction between a BH3 domain, that of Bim, with Bax. Here, we review these intriguing observations and discuss their implications for our understanding of how the BH3-only proteins initiate apoptosis.
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Abbreviations
- BH:
-
Bcl-2 homology domain
- HSQC:
-
heteronuclear single quantum coherence
- NMR:
-
nuclear magnetic resonance
- PRE:
-
paramagnetic relaxation enhancement
- PDB:
-
protein data bank
- SAHB:
-
stabilized α-helix of Bcl-2 domains
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Acknowledgements
Work in our laboratories is supported by grants and fellowships from the Australian NHMRC, the US NCI, the Leukemia and Lymphoma Society, the Cancer Council of Victoria and the Victorian State Government. We thank our colleagues for many stimulating discussions.
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Czabotar, P., Colman, P. & Huang, D. Bax activation by Bim?. Cell Death Differ 16, 1187–1191 (2009). https://doi.org/10.1038/cdd.2009.83
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DOI: https://doi.org/10.1038/cdd.2009.83
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