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Perspectives

Controlling the cell death mediators Bax and Bak: puzzles and conundrums

Jamie I. Fletcher and David C.S. Huang

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In spite of the available genetic, biochemical and structural data, precisely how the initiators of apoptosis, the BH3-only proteins, trigger Bax and Bak to cause organellar damage remains highly contentious. A widely accepted model suggests that these two critical mediators of apoptosis remain inert until they are directly activated by a subclass of BH3-only proteins including Bim, Bid, and possibly Puma. However, our recent work showed that these death ligands are dispensable for apoptosis to proceed, whereas neutralization of the pro-survival Bcl 2 proteins is essential. These findings challenge current assumptions about how the BH3-only proteins provoke apoptotic cell death and have implications for the development of therapeutics to interfere with the Bcl 2 regulated apoptotic pathway for treating diseases such as cancer.

Authors

Jamie I. Fletcher

The Walter and Eliza Hall Institute of Medical Research; Victoria, Australia

David C.S. Huang

The Walter and Eliza Hall Institute of Medical Research; Victoria, Australia

Purchase article for $19

Subscribe to this journal for $129/year