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Cancer Lett. 2003 May 8;194(1):81-9.

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

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  • 1GSF-National Research Center for Environment and Health, Institute of Radiobiology, Ingolstaedter Landstr 1, D-85764, Neuherberg, Germany. eichholtz@gsf.de


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.

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