Tumor necrosis factor-alpha (TNFalpha) is an inflammatory cytokine, that activates either cell survival (e.g.,inflammation, proliferation) or cell death upon association with TNF receptor 1 (TNFR1). Stimuli and the cellular context dictate cell fate decisions between survival and death which rely on tightly regulated mechanisms with checkpoints on many levels. TNFR1-mediated NFkappaB activation leads to the pro-survival transcriptional program that is both anti-apoptotic and highly proinflammatory. The constitutive NFkappaB or AP1 activation may lead to excessive inflammation which has been associated with a variety of aggressive tumor types (Jackson-Bernitsas DG et al. 2007; Zhang JY et al. 2007). Thus, the tight regulation of TNFalpha:TNFR1 signaling is required to ensure the appropriate cell response to stimuli.