Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1.

Bcl-x(L), an antiapoptotic Bcl-2 family member, is postulated to function at multiple stages in the cell death pathway. The possibility that Bcl-x(L) inhibits cell death at a late (postmitochondrial) step in the death pathway is supported by this report of a novel apoptosis inhibitor, Aven, which binds to both Bcl-x(L) ...
and the caspase regulator, Apaf-1. Identified in a yeast two-hybrid screen, Aven is broadly expressed and is conserved in other mammalian species. Only those mutants of Bcl-x(L)that retain their antiapoptotic activity are capable of binding Aven. Aven interferes with the ability of Apaf-1 to self-associate, suggesting that Aven impairs Apaf-1-mediated activation of caspases. Consistent with this idea, Aven inhibited the proteolytic activation of caspases in a cell-free extract and suppressed apoptosis induced by Apaf-1 plus caspase-9. Thus, Aven represents a new class of cell death regulator.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, Apoptotic Protease-Activating Factor 1, Carrier Proteins, Caspase 9, Caspases, Cell Line, Dimerization, Enzyme Activation, Humans, Membrane Proteins, Mice, Molecular Sequence Data, Mutation, Protein Binding, Protein Structure, Quaternary, Proteins, Proto-Oncogene Proteins c-bcl-2, RNA, Messenger, Tissue Distribution, Transfection, bcl-X Protein
Mol. Cell
Date: Jul. 01, 2000
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