Abstract
We report here the purification of a cytosolic protein that induces cytochrome c release from mitochondria in response to caspase-8, the apical caspase activated by cell surface death receptors such as Fas and TNF. Peptide mass fingerprinting identified this protein as Bid, a BH3 domain-containing protein known to interact with both Bcl2 and Bax. Caspase-8 cleaves Bid, and the COOH-terminal part translocates to mitochondria where it triggers cytochrome c release. Immunodepletion of Bid from cell extracts eliminated the cytochrome c releasing activity. The cytochrome c releasing activity of Bid was antagonized by Bcl2. A mutation at the BH3 domain diminished its cytochrome c releasing activity. Bid, therefore, relays an apoptotic signal from the cell surface to mitochondria.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / physiology*
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BH3 Interacting Domain Death Agonist Protein
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Carrier Proteins / metabolism*
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Caspase 8
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Caspase 9
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Caspases*
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Cysteine Endopeptidases / metabolism
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Cytochrome c Group / metabolism*
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HeLa Cells
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Humans
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Mice
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Mitochondria, Liver / metabolism*
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Molecular Sequence Data
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Cell Surface / metabolism*
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Sequence Analysis
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Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
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fas Receptor / metabolism*
Substances
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BH3 Interacting Domain Death Agonist Protein
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BID protein, human
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Bid protein, mouse
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Carrier Proteins
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Cytochrome c Group
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Cell Surface
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fas Receptor
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CASP8 protein, human
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CASP9 protein, human
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Casp8 protein, mouse
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Casp9 protein, mouse
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Caspase 8
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Caspase 9
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Caspases
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Cysteine Endopeptidases