Identification of a novel tumor necrosis factor-α-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein

We report here the isolation and characterization of a novel tumor necrosis factor-alpha (TNF-alpha)-inducible gene, SCC-S2, Based on the nucleotide sequence, the SCC-SP open reading frame contains a sequence in the amino terminus that shows a significant homology to death effector domain II of cell death regulatory protein, Fas-associated death domain-like interleukin-1 beta-converting enzyme-inhibitory protein (FLIP). Unlike FLIP, the SCC-SS open reading frame contains only one death effector domain and lacks the carboxyl-terminal caspase-like homology domain, raising the possibility that SCC-S2 may be a novel member of the FLIP family. SCC-S2 mRNA expression is found in most normal tissues and malignant cells. The steady state level of SCC-S2 mRNA is significantly induced by TNF-a in different tumor cells (TNF-alpha at 20 ng/ml for 3 h: A549, similar to 2-9-fold; SKOV-3, similar to 3-fold; PCI-04A, similar to 3-6-fold), TNF-alpha treatment (100 ng/ml, 4 h) of HeLa cells transiently transfected with FLAG epitope-tagged SCC-S2 cDNA or expression vector alone led to an increase in the number of apoptotic cells as compared with the untreated counterpart. Interestingly, however, SCC-S2 transfectants revealed a significant decrease in the number of apoptotic cells as compared with the vector transfectants (p < 0.001). These data implicate a role of SCC-S2 as a negative mediator of apoptosis in certain cell, types.