Apoptosis regulatory protein Siva is a protein that in humans is encoded by the SIVA1gene.[1][2]
This gene encodes a protein with an important role in the apoptotic (programmed cell death) pathway induced by the CD27 antigen, a member of the tumor necrosis factor receptor (TFNR) superfamily. The CD27 antigen cytoplasmic tail binds to the N-terminus of this protein. Two alternatively spliced transcript variants encoding distinct proteins have been described.[2]
Siva protein is a zinc-containing intracellular ligand of the CD4 receptor that promotes HIV-1 envelope-induced apoptosis in T-lymphoid cells. Recent research has demonstrated that Siva is a direct transcriptional target for the tumor-suppressors p53 and E2F1. [3]
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Chu F, Borthakur A, Sun X, et al. (2004). "The Siva-1 putative amphipathic helical region (SAH) is sufficient to bind to BCL-XL and sensitize cells to UV radiation induced apoptosis". Apoptosis. 9 (1): 83–95. doi:10.1023/B:APPT.0000012125.01799.4c. PMID14739602.
Py B, Slomianny C, Auberger P, et al. (2004). "Siva-1 and an alternative splice form lacking the death domain, Siva-2, similarly induce apoptosis in T lymphocytes via a caspase-dependent mitochondrial pathway". J. Immunol. 172 (7): 4008–17. doi:10.4049/jimmunol.172.7.4008. PMID15034012.
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Chu F, Barkinge J, Hawkins S, et al. (2005). "Expression of Siva-1 protein or its putative amphipathic helical region enhances cisplatin-induced apoptosis in breast cancer cells: effect of elevated levels of BCL-2". Cancer Res. 65 (12): 5301–9. doi:10.1158/0008-5472.CAN-04-3270. PMID15958577.
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Nestler M, Martin U, Hortschansky P, et al. (2006). "The zinc containing pro-apoptotic protein siva interacts with the peroxisomal membrane protein pmp22". Mol. Cell. Biochem. 287 (1–2): 147–55. doi:10.1007/s11010-005-9082-6. PMID16683188.
Severino A, Abbruzzese C, Manente L, et al. (2007). "Human papillomavirus-16 E7 interacts with Siva-1 and modulates apoptosis in HaCaT human immortalized keratinocytes". J. Cell. Physiol. 212 (1): 118–25. doi:10.1002/jcp.21011. PMID17348035.