Siva-1 binds to and inhibits BCL-XL-mediated protection against UV radiation-induced apoptosis

Li Xue, Fei Chu, Yuan Cheng, Xiangjie Sun, Alip Borthakur, Manjunath Ramarao, Pramod Pandey, Mei Wu, Stuart F. Schlossman, Kanteti V S Prasad

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

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-XL, prompted us to test for a potential interaction between Siva-1 and BCL-XL. Here, we show that Siva-1 binds to and inhibits BCL-XL-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-XL and sensitizing cells to UV radiation. Natural complexes of Siva-1/BCL-XL are detected in HUT78 and murine thymocyte, suggesting a potential role for Siva-1 in regulating T cell homeostasis.

Original languageEnglish (US)
Pages (from-to)6925-6930
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number10
DOIs
StatePublished - May 14 2002

ASJC Scopus subject areas

  • General

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