Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of Fas-associated death domain-like interleukin-1 beta-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 s equence, the SCC-SP open reading frame contains a sequence in the amino ter minus that shows a significant homology to death effector domain II of cell death regulatory protein, Fas-associated death domain-like interleukin-1 b eta-converting enzyme-inhibitory protein (FLIP). Unlike FLIP, the SCC-SS op en reading frame contains only one death effector domain and lacks the carb oxyl-terminal caspase-like homology domain, raising the possibility that SC C-S2 may be a novel member of the FLIP family. SCC-S2 mRNA expression is fo und in most normal tissues and malignant cells. The steady state level of S CC-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) o f HeLa cells transiently transfected with FLAG epitope-tagged SCC-S2 cDNA o r expression vector alone led to an increase in the number of apoptotic cel ls 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 im plicate a role of SCC-S2 as a negative mediator of apoptosis in certain cel l, types.