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Murine Siva-1 and Siva-2, alternate splice forms of the mouse Siva gene, both bind to CD27 but differentially transduce apoptosis

Abstract

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 proapoptotic 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.

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Acknowledgements

KVS Prasad is the recipient of Claudia Adams Barr Award. This research was partly funded by the NIH grant (GM56706). We thank Drs J Duke-Cohan, Mei Wu, G Weber and H Saito for their helpful advice.

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Yoon, Y., Ao, Z., Cheng, Y. et al. Murine Siva-1 and Siva-2, alternate splice forms of the mouse Siva gene, both bind to CD27 but differentially transduce apoptosis. Oncogene 18, 7174–7179 (1999). https://doi.org/10.1038/sj.onc.1203144

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