Abstract
We identified and cloned a novel murine member of the pro-apoptotic Bcl-2 family. This protein, designated Blk, is structurally and functionally related to human Bik and localized to the mitochondrial membrane. Blk contains a conserved BH3 domain and can interact with the anti-apoptotic proteins Bcl-2 and Bcl-xL. Ectopic expression of Blk in mammalian cells induces apoptosis, which can be inhibited by mutations in the BH3 domain and by overexpression of Bcl-2 or Bcl-xL but not by CrmA. The apoptotic activity of Blk is also inhibited by a dominant negative caspase-9, suggesting that Blk induces apoptosis through activation of the cytochrome c-Apaf-1-caspase-9 pathway.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Apoptosis / genetics*
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Apoptosis Regulatory Proteins
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Cloning, Molecular
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Humans
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Membrane Proteins / genetics*
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism
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Mice
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Mitochondria / metabolism
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Mitochondrial Proteins*
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Molecular Sequence Data
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Organ Specificity
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Proteins / genetics
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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bcl-X Protein
Substances
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Adaptor Proteins, Signal Transducing
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Apoptosis Regulatory Proteins
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BCL2L1 protein, human
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BIK protein, human
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Bcl2l1 protein, mouse
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Bik protein, mouse
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Carrier Proteins
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DNA, Complementary
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Membrane Proteins
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Mitochondrial Proteins
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Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-X Protein