Overexpression of the 'silencer of death domain', SODD/BAG-4, modulates both TNFR1- and CD95-dependent cell death pathways

Cancer Lett. 2003 May 8;194(1):81-9. doi: 10.1016/s0304-3835(03)00009-0.


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

  • Adaptor Proteins, Signal Transducing*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Antigens, CD / metabolism*
  • Apoptosis*
  • Blotting, Western
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism*
  • Carrier Proteins / physiology*
  • DNA, Complementary / metabolism
  • DNA-Binding Proteins
  • Fas Ligand Protein
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Ligands
  • Membrane Glycoproteins / metabolism
  • Mice
  • Oligomycins / pharmacology
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I
  • Signal Transduction
  • Subcellular Fractions
  • Transcription Factors
  • Transfection
  • fas Receptor / biosynthesis*
  • fas Receptor / metabolism


  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • BAG4 protein, human
  • BCL2-associated athanogene 1 protein
  • Bag4 protein, mouse
  • Carrier Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Ligands
  • Membrane Glycoproteins
  • Oligomycins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Transcription Factors
  • fas Receptor
  • Adenosine Triphosphate