Abstract
The Drosophila spinster (spin) gene product is required for programmed cell death in the nervous and reproductive systems. We have identified a human homologue of the Drosophila spin gene product (HSpin1). HSpin1 bound to Bcl-2 and apoptosis regulator Bcl-X (Bcl-xL), but not to proapoptotic members such as Bcl-2-associated X protein and Bcl-2 homologous antagonist killer, in cells treated with TNF-alpha. Exogenous expression of HSpin1 resulted in the cell death without inducing a release of cytochrome c from mitochondria. Overexpression of Bcl-xL inhibited the HSpin1-induced cell death. Interestingly, a necrosis inhibitor, pyrrolidine dithiocarbomate, but not the pancaspase inhibitors, carbobenzoxy-VAD-fluoromethyl ketone and p35, blocked the HSpin1-induced cell death. HSpin1-induced cell death increases autophagic vacuole and mature form of cathepsin D, suggesting a novel caspase-independent cell death, which is link to autophagy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Autophagy / genetics*
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Caspase Inhibitors
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Caspases / metabolism
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Cathepsin D / metabolism
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Cell Cycle Proteins
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Cell Death / genetics
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Enzyme Inhibitors / pharmacology
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HeLa Cells
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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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Membrane Transport Proteins
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Microtubule-Associated Proteins
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Phosphoproteins
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Protein Binding / physiology
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Protein Structure, Tertiary / physiology
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
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Pyrrolidines / pharmacology
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Thiocarbamates / pharmacology
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / pharmacology
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Vacuoles / drug effects
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Vacuoles / metabolism
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bcl-X Protein
Substances
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BCL2L1 protein, human
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Caspase Inhibitors
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Cell Cycle Proteins
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Enzyme Inhibitors
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Membrane Proteins
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Membrane Transport Proteins
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Microtubule-Associated Proteins
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Phosphoproteins
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Proto-Oncogene Proteins c-bcl-2
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Pyrrolidines
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Thiocarbamates
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Tumor Necrosis Factor-alpha
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bcl-X Protein
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spindlin
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pyrrolidine dithiocarbamic acid
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Caspases
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Cathepsin D