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

Abstract

We report here the isolation and characterization of a novel tumor necrosis factor-α (TNF-α)-inducible gene,<i>SCC-S2</i>. Based on the nucleotide sequence, the SCC-S2 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-1β-converting enzyme-inhibitory protein (FLIP). Unlike FLIP, the SCC-S2 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. <i>SCC-S2</i> mRNA expression is found in most normal tissues and malignant cells. The steady state level of<i>SCC-S2</i> mRNA is significantly induced by TNF-α in different tumor cells (TNF-α at 20 ng/ml for 3 h: A549, ∼2–9-fold; SKOV-3, ∼3-fold; PCI-04A, ∼3–6-fold). TNF-α treatment (100 ng/ml, 4 h) of HeLa cells transiently transfected with FLAG epitope-tagged <i>SCC-S2</i> cDNA or expression vector alone led to an increase in the number of apoptotic cells as compared with the untreated counterpart. Interestingly, however,<i>SCC-S2</i> transfectants revealed a significant decrease in the number of apoptotic cells as compared with the vector transfectants (<i>p</i> < 0.001). These data implicate a role of SCC-S2 as a negative mediator of apoptosis in certain cell types.