PMID:12011449

Citation	Xue, L, Chu, F, Cheng, Y, Sun, X, Borthakur, A, Ramarao, M, Pandey, P, Wu, M, Schlossman, SF and Prasad, KV (2002) Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis. Proc. Natl. Acad. Sci. U.S.A. 99:6925-30
Abstract	We previously cloned Siva-1 by using the cytoplasmic tail of CD27, a member of the tumor necrosis factor receptor family, as the bait in the yeast two-hybrid system. The Siva gene is organized into four exons that code for the predominant full-length Siva-1 transcript, whereas its alternate splice form, Siva-2, lacks exon 2 coding sequence. Various groups have demonstrated a role for Siva-1 in several apoptotic pathways. Interestingly, the proapoptotic properties of Siva-1 are lacking in Siva-2. The fact that Siva-1 is partly localized to mitochondria despite the absence of any mitochondrial targeting signal, it harbors a 20-aa-long putative amphipathic helical structure that is absent in Siva-2, and that its expression is restricted to double-positive (CD3(+), CD4(+), CD8(+)) thymocytes like BCL-X(L), prompted us to test for a potential interaction between Siva-1 and BCL-X(L). Here, we show that Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis. Indeed, the unique amphipathic helical region (SAH) present in Siva-1 is required for its binding to BCL-X(L) and sensitizing cells to UV radiation. Natural complexes of Siva-1/BCL-X(L) are detected in HUT78 and murine thymocyte, suggesting a potential role for Siva-1 in regulating T cell homeostasis.
Links	PubMed PMC124505 Online version:10.1073/pnas.102182299
Keywords	Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins; COS Cells; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Line, Transformed; Cercopithecus aethiops; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins; Molecular Sequence Data; Protein Isoforms/genetics; Protein Isoforms/metabolism; Proto-Oncogene Proteins c-bcl-2/metabolism; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Ultraviolet Rays; bcl-X Protein
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