| First Author | Xue L | Year | 2002 |
| Journal | Proc Natl Acad Sci U S A | Volume | 99 |
| Issue | 10 | Pages | 6925-30 |
| PubMed ID | 12011449 | Mgi Jnum | J:127189 |
| Mgi Id | MGI:3763309 | Doi | 10.1073/pnas.102182299 |
| Citation | Xue L, et al. (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(10):6925-30 |
| abstractText | 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. |
