Abstract
Human Bcl-2 is located in multiple intracellular membranes when expressed in MDCK and Rat-1/myc cells. We restricted expression to the endoplasmic reticulum or mitochondria by exchanging the Bcl-2 carboxy-terminal insertion sequence for an equivalent sequence from cytochrome b5 or ActA, respectively. MDCK cells are protected from serum deprivation-induced apoptosis by both wild-type Bcl-2 and the mutant targeted to mitochondria but not by the mutant targeted to endoplasmic reticulum. In contrast, when expressed in Rat-1/myc cells, the Bcl-2 mutant located at the endoplasmic reticulum is more effective than that targeted to mitochondria. In MDCK cells both mutants bind Bax as effectively as wild-type, demonstrating that Bax binding is not sufficient to prevent apoptosis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / physiology*
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Cell Line
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Dogs
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Endoplasmic Reticulum / metabolism
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Epithelium / metabolism
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Fibroblasts / metabolism
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Humans
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Intracellular Membranes / metabolism*
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Kidney / cytology
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Mice
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Mitochondria / metabolism
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Molecular Sequence Data
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Organ Specificity
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Proto-Oncogene Proteins / metabolism
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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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Proto-Oncogene Proteins c-myc / metabolism
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Rats
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Recombinant Fusion Proteins / metabolism
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bcl-2-Associated X Protein
Substances
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BAX protein, human
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Bax protein, mouse
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Bax protein, rat
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-myc
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Recombinant Fusion Proteins
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bcl-2-Associated X Protein