FIGURE 9.

Role of COUP-TFI during TNFα-induced apoptosis. Solid and dashed lines represent known and hypothesized events, respectively. Note that treatment with either TNFα or CHX reduces endogenous COUP-TFI protein levels, which relieves repression of the TNFAIP8 promoter, resulting in inhibition of caspase-8 activation and reduced apoptosis. Conversely, ectopically overexpressed COUP-TFI represses TNFAIP8 expression in a manner that is insensitive TNFα, resulting in loss of TNFAIP8 protein and increased sensitivity to TNFα-induced apoptosis. Thus, COUP-TFI may play a central role in the sensitivity of a cell to TNFα-induced apoptosis.