Bax activation by Bim?
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.
Czabotar
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PE
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. czabotar@wehi.edu.au
Colman
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PM
Huang
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DC
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C474007:Bax protein (53-86); D000072224:Bcl-2-Like Protein 11; D008565:Membrane Proteins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein