A crucial role for p80 TNF-R2 in amplifying p60 TNF-R1 apoptosis signals in T lymphocytes.
Tumor necrosis factor-alpha (TNF-alpha) can elicit many cellular responses including programmed cell death or apotosis. TNF-alpha-induced apoptosis has been largely attributed to the p60 TNF-R1 receptor. The role of p80 in TNF-alpha-mediated apoptosis is largely unknown. We now present evidence that signaling through p80 switches on the previously dormant apoptotic machinery associated with p60. This effect on p60-associated apoptosis involves the proximal activation of caspases and proceeds in the presence of strong NF-kappaB induction. We evaluated the role of TRAF2 in p80-assisted apoptosis and found that a decrease in TRAF2 protein occurs with p80 but not p60 stimulation. However, the decrease in TRAF2 protein can be dissociated from apoptosis in the presence of a caspase inhibitor. Hence, one means by which p80 TNF-R2 regulates apoptosis is through its ability to amplify internally apoptotic signal transduction from p60 TNF-R1.
Chan
F K
FK
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1892, USA.
Lenardo
M J
MJ
D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha