Abstract
The involvement of SODD/BAG-4 was studied in TNFR1 signaling, using SODD/BAG-4- overexpressing HeLa cells as a cellular model. Stable transfection of a SODD/BAG-4 cDNA leads to increased levels of the full-length 70-kDa protein and additional C-terminal fragments as well as altered expression of BAG-1. Concomitantly, the protein amounts of both the TNFR1 and, unexpectedly, the CD95 receptors are elevated. These biochemical changes are paralleled and confirmed by a reduced cellular sensitivity to treatment with extracellular TNFalpha and CD95 ligand. Moreover, ATP depletion by oligomycin is less toxic in SODD/BAG-4 overexpressing clones. The radiosensitivity is reduced in some, but not in all of these clones. Our results indicate that SODD/BAG-4 is not only a silencer of TNFR1 but also a modulator of CD95 activity, regulating the balance of both death-promoting and -depressing signals.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adenosine Triphosphate / metabolism
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Animals
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Antigens, CD / metabolism*
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Apoptosis*
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Blotting, Western
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Carrier Proteins / biosynthesis
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Carrier Proteins / metabolism*
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Carrier Proteins / physiology*
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DNA, Complementary / metabolism
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DNA-Binding Proteins
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Fas Ligand Protein
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Gene Silencing
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HeLa Cells
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Humans
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Ligands
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Membrane Glycoproteins / metabolism
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Mice
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Oligomycins / pharmacology
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Precipitin Tests
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Protein Structure, Tertiary
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Receptors, Tumor Necrosis Factor / metabolism*
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Receptors, Tumor Necrosis Factor, Type I
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Signal Transduction
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Subcellular Fractions
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Transcription Factors
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Transfection
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fas Receptor / biosynthesis*
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fas Receptor / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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BAG4 protein, human
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BCL2-associated athanogene 1 protein
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Bag4 protein, mouse
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Carrier Proteins
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DNA, Complementary
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DNA-Binding Proteins
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FASLG protein, human
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Fas Ligand Protein
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Fasl protein, mouse
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Ligands
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Membrane Glycoproteins
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Oligomycins
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Transcription Factors
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fas Receptor
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Adenosine Triphosphate