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CSR1 inhibits XIAP
Author(s) -
Luo Jianhua,
Zheng Zhong-Liang,
Yu Yan P
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.397.3
Subject(s) - xiap , inhibitor of apoptosis , programmed cell death , caspase , apoptosis , chemistry , microbiology and biotechnology , mutant , in vitro , cancer research , biology , biochemistry , gene
CSR1 is a tumor suppressor gene located at 8p21, a region that is frequently deleted in a variety of human malignancies. Previous studies indicated that expression of CSR1 induced cell death. In this study, we identified that CSR1 interacted with XIAP through a Yeast Two‐hybrid screening analysis. In vitro and in vivo analyses indicate that the C‐terminus of CSR1 binds with XIAP with high affinity. Through a series of in vitro recombinant protein binding analyses, the XIAP binding motif in CSR1 was determined located at amino acids 513–572. Knocking down of XIAP enhanced the CSR1 induced cell death, while over‐expression of XIAP antagonized CSR1's activity. The binding CSR1 with XIAP enhanced caspase‐9 and caspase‐3 protease activities. Mutant CSR1 that does not bind XIAP contained dramatically reduced cell death induction activity. XIAP mutant that does not interact with caspase‐9 had no impact on CSR1 induced cell death. As a result, this study elucidates a novel mechanism of cell death through relieving XIAP from inhibiting caspase activity by binding with a tumor suppressor.