Murine Siva-1 and Siva-2, alternate splice forms of the mouse Siva gene, both bind to CD27 but differentially transduce apoptosis.
CD27, a member of the TNFR family known to provide essential co-stimulatory signals for T cell growth and B cell Ig synthesis, can also mediate cell death. Using the CD27 cytoplasmic tail as the bait in yeast two hybrid assay, we previously cloned human Siva, a pro-apoptotic molecule. Here we report the characterization of the mouse Siva gene as a 4 kb sequence containing 4 exons and 3 introns. RT-PCR has revealed the presence of two forms of mouse Siva mRNA, the longer full length form Siva-1 and the shorter Siva-2 lacking the sequence coded by exon 2. Immunoblotting with anti-Siva (human) antibodies clearly demonstrate the presence of both Siva-1 and Siva-2. Cotransfection experiments in 293T cells reveal that mouse CD27 receptor can interact with both forms of Siva. Although mouse Siva-1 can trigger apoptosis in Rat-1 cells and in some of the mouse cell lines in transient transfection experiments, similar to the observation made with human Siva, intriguingly its alternate splice form, Siva-2 appears to be much less toxic. It is therefore likely that Siva-2 could regulate the function of Siva-1.
Yoon
Y
Y
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Ao
Z
Z
Cheng
Y
Y
Schlossman
S F
SF
Prasad
K V
KV
D016475:3T3 Cells; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014161:Transduction, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; C106549:SIVA1 protein, human; C484569:Siva protein, mouse; C484570:Siva1 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7