Abstract
Epithelial cells require adhesion to the extracellular matrix for survival, and in the absence of adhesion they undergo apoptosis (anoikis). This is distinct from apoptosis induced by extracellular death ligands, such as tumor necrosis factor, which result in direct activation of caspase 8. Bid is a member of the BH3-only subfamily of the Bcl-2 proteins and is important for most cell types to apoptose in response to Fas and tumor necrosis factor receptor activation. Caspase 8 cleaves full-length Bid, resulting in truncated p15 tBid. p15 tBid is potently apoptotic and activates the multidomain Bcl-2 protein, Bax, resulting in release of cytochrome c from mitochondria. We have previously shown that Bax rapidly translocates from the cytosol to mitochondria following loss of adhesion and that this is required for anoikis. We have now examined the role of Bid in anoikis. Bid translocates to mitochondria with identical kinetics as Bax. Although Bid is required for anoikis, it does not require proteolytic cleavage by caspase 8. Furthermore, it does not require Bid to interact directly with other Bcl-2 family proteins, such as Bax. Our data indicate that Bid is important for regulating apoptosis via the intrinsic pathway and has implications for how Bid may fulfill that role.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anoikis*
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Apoptosis
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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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Caspases / metabolism
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Cell Adhesion
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Cell Death
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Cross-Linking Reagents / pharmacology
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Cytochromes c / metabolism
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Cytosol / metabolism
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DNA, Complementary / metabolism
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Epithelial Cells / metabolism
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Epitopes
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Extracellular Matrix / metabolism
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Gene Library
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Green Fluorescent Proteins
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Kinetics
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Ligands
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Luminescent Proteins / metabolism
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Mice
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Microscopy, Fluorescence
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Mitochondria / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Structure, Tertiary
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Protein Transport
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA, Small Interfering / metabolism
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Subcellular Fractions / metabolism
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Transfection
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Tumor Necrosis Factor-alpha / metabolism
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bcl-2-Associated X Protein
Substances
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BH3 Interacting Domain Death Agonist Protein
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Bax protein, mouse
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Bid protein, mouse
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Carrier Proteins
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Cross-Linking Reagents
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DNA, Complementary
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Epitopes
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Ligands
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Luminescent Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Small Interfering
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Tumor Necrosis Factor-alpha
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bcl-2-Associated X Protein
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Green Fluorescent Proteins
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Cytochromes c
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Phosphatidylinositol 3-Kinases
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Casp8 protein, mouse
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Caspase 8
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Caspases