期刊
CELL
卷 135, 期 6, 页码 1074-1084出版社
CELL PRESS
DOI: 10.1016/j.cell.2008.11.010
关键词
-
资金
- Canadian Institute of Health Research (CIHR) [FRN12517]
- Tier I Canada Research Chair in Membrane Biogenesis
In normal circumstances, the Bcl-2 family dutifully governs when cells die. However, the rules of engagement between the pro- and antiapoptotic family members are still contested, and how Bax is transformed from a cytosolic monomer to an outer mitochondrial membrane-permeabilizing oligomer is unclear. With fluorescence techniques and an in vitro system, the combination of tBid and Bax produced dramatic membrane permeabilization. The membrane is not a passive partner in this process beause membranes are required for the protein-protein interactions to occur. Simultaneous measurements of these interactions revealed an ordered series of steps required for outer membrane permeabilization: ( 1) tBid rapidly binds to membranes, where ( 2) tBid interacts with Bax, causing ( 3) Bax insertion into membranes and ( 4) oligomerization, culminating in ( 5) membrane permeabilization. Bcl-XL prevents membrane- bound tBid from binding Bax. Bad releases tBid from Bcl-XL, restoring both tBid binding to Bax and membrane permeabilization.
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