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- 1beta-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-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-1beta-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. 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-alpha in different tumor cells (TNF-alpha at 20 ng/ml for 3 h: A549, approximately 2-9-fold; SKOV-3, approximately 3-fold; PCI-04A, approximately 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.
Kumar
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Department of Radiation Medicine, Lombardi Cancer Center, Georgetown University Medical Center, Washington, D.C. 20007, USA.
Whiteside
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Kasid
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018076:DNA, Complementary; D053200:Fas-Associated Death Domain Protein; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D011506:Proteins / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D017386:Sequence Homology, Amino Acid; D015843:Serpins / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014764:Viral Proteins
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D015843:Serpins; C404190:TNFAIP8 protein, human; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; C074641:interleukin-1beta-converting enzyme inhibitor